Biomedical subjects

A Boyde

Publications and source records attributed to A Boyde.

At least 37 records · Page 2Linked to original sources

PubMed2000

Functions of cathepsin K in bone resorption. Lessons from cathepsin K deficient mice.

Cathepsin K is a cysteine proteinase expressed predominantly in osteoclasts. Cathepsin K cleaves key bone matrix proteins and is believed to play an important role in degrading the organic phase of bone during bone resorption. Pycnodysostosis, an autosomal recessive osteosclerosing skeletal disorder has recently been shown to result from mutations in the cathepsin K gene. Cathepsin K deficient mice generated by targeted disruption of this proteinase phenocopy many aspects of pycnodysostosis. They display an osteopetrotic phenotype with excessive trabeculation of the bone-marrow space accompanied by an altered ultrastructural appearance of the cathepsin K deficient osteoclasts. These cells also demonstrate an impaired resorptive activity in vitro. In contrast to other forms of osteopetrosis, which are due to disrupted osteoclastogenesis, cathepsin K deficiency is associated with an inhibition of osteoclast activity. Taken together the phenotype of cathepsin K knockout mice underlines the importance of this proteinase in bone remodelling.

Animals↗

PubMed2000

Osteoclastic resorption of equine cranial and postcranial bone in vitro.

To address possible differences in the resorbability of cranial and postcranial bone, slices of equine frontal bone and leg (first phalanx or third metacarpus) were seeded with embryonic chick bone cells and cultured for 20-24h. After removing the cells and drying the specimens, the areas and volumes of more than 800 resorption pits in each set were measured using a video-rate reflection confocal microscope system. Relative mineralization densities were determined by quantitative electron backscattering analysis. The mean mineralization density was greater in the leg bone, but the mean depths for resorption pits in frontal bone were smaller (median volume/area ratios, experiment 1 and experiment 2: 1.98 microm frontal and 3.79 microm leg versus 2.70 microm and 4.20 microm, respectively; P < 0.0001, Mann-Whitney), even though the areas were greater in the frontal (medians, 286 microm2 and 324 microm2, versus 242 microm2 and 201 microm2; P < 0.0001). This study has shown a difference between cranial and postcranial equine bone in the shape and size of resorption pits formed in vitro. Overall, it has shown that cranial bone may be resorbed at least as readily as postcranial bone. This result is counter to the clinical impression that cranial bone has a greater staying power than postcranial bone when used as a grafting material.

Animals↗

PubMed2000

Structure and mineralisation density of antler and pedicle bone in red deer (Cervus elaphus L.) exposed to different levels of environmental fluoride: a quantitative backscattered electron imaging study.

The structure and relative degree of mineralisation of antler and pedicle bone of yearling red deer stags exposed either to low or high levels of environmental fluoride were determined by digital quantitative backscattered electron (BSE) imaging. Bone fluoride content (BFC) in antlers (845 +/- 86 mg F-/kg ash, arithmetic mean +/- S.E.M.) and pedicles (1448 +/- 154 mg F-/kg ash) of deer from a highly fluoride polluted area in North Bohemia (Czech Republic) were significantly higher (P < 0.001) than those of controls from uncontaminated regions in West Germany (antlers: 206 +/- 41, pedicles: 322 +/- 52 mg F-/kg ash). Mean (56.5 +/- 4.5%) and maximum (84.9 +/- 2.1%) mineralised bone area of the control antlers significantly (P < 0.05 and P < 0.001, respectively) exceeded the corresponding values for the N. Bohemian deer (43.3 +/- 1.3 and 73.3 +/- 1.9%, respectively), while the pedicles from the 2 groups did not differ significantly. In the pooled antler samples (n = 18), negative correlations existed between BFC and mean (r(s) = -0.62, P < 0.01) as well as maximum (r(s) = -0.69, P < 0.01) mineralised bone area. Morphological imaging revealed a decreased width and an increased porosity of the antler cortex in the N. Bohemian specimens. Mean (148.5 +/- 1.7) and maximum (154.2 +/- 1.7) BSE-signal intensities (= grey levels; range between a monobrominated (grey level 0) and a monoiodinated (grey level 255) dimethacrylate resin standard) of the antlers from the controls were significantly higher than those of the N. Bohemian deer (140.7 +/- 2.1 and 145.7 +/- 2.2, respectively; P < 0.05 for both comparisons). In the pooled antler samples, negative correlations between BFC and mean (r(s) = -0.51, P < 0.05) as well as maximum (r(s) = -0.52, P < 0.05) BSE-signal intensities were observed. No significant differences in mineralisation density parameters were found for the 2 pedicle samples, and BFC and mineralisation density of the pooled pedicles were uncorrelated. Morphological imaging revealed bone mottling (denoting increased remodelling activity) and frequent occurrence of apparently increased osteocyte lacunae in some of the pedicles from the N. Bohemian deer. It is concluded that the reduced amount of mineralised bone in, and the lower mineralisation density of, the N. Bohemian antlers resulted from a fluoride induced disturbance of bone mineralisation. The rapid growth of antlers leads both to a high mineral demand and a high rate of fluoride uptake during antlerogenesis. This, and the limited lifespan of antlers, which does not allow for a compensation of a delay in the onset or progression of the mineralisation process, renders antler bone particularly susceptible to fluoride. Antlers are therefore considered a useful model for studying fluoride effects on bone formation. Furthermore, analysis of cast antlers enables a noninvasive monitoring of environmental pollution by fluorides.

Animals↗

PubMed1999

Mineralization density and apparent density of bone in cranial and postcranial sites in the aging human.

This study addressed the question whether bone density of the mandible reflects bone density at other sites. Samples of cranial bone (mandible and parietal bone) and postcranial bone (fourth lumbar vertebral body, iliac crest and femoral neck) from 14 individuals aged 69-96 years were compared. One slice from each bone was used for apparent density determination by weighing it and dividing by a volume calculated as the product of section thickness and the mean area of the two sides of the section. Another slice was embedded in poly(methylmethacrylate) and micromilled to study the mineralization density by quantitative backscattered electron (QBSE) analysis in a scanning electron microscope, rescaling image histograms to the signal range from a monobrominated (0) to a monoiodinated (255) dimethacrylate resin standard. Mandibular QBSE values (e.g., at the mental foramen region 178.0) were much higher (p < 0.0001, paired t-test) than at other sites (parietal, 170.1; fourth lumbar vertebra (L4), 155.4; iliac crest (IC), 155.2; femoral neck (FN), 160.7 units), and correlated only with parietal bone (r = 0.70). Mean QBSE values for the postcranial sites were correlated (L4 with IC, r = 0.63; L4 with FN, r = 0.88; IC with FN, r = 0.59) as were the apparent density values (L4 with IC, r = 0.87; L4 with FN, r = 0.75; IC with FN, r = 0.80). Neither the apparent density nor the mineralization density of the mandible showed a correlation with values for the postcranial sites. The condition of bone in the elderly mandible should not be used to infer status at postcranial sites.

Aged↗

PubMed1999

The microscopic structure of bone in normal children and patients with osteogenesis imperfecta: a survey using backscattered electron imaging.

The microstructure of iliac crest biopsies from normal children or from those afflicted with osteogenesis imperfecta (OI) has not previously been studied to determine the tissue histology in the context of the degree of mineralization. The material in this study comprised 112 iliac crest biopsies from children aged 1.9-22.9 years. Fifty-eight were reference biopsies taken from children with no bone disease and the remainder were biopsies from children diagnosed as having OI (23 were Type I, 8 Type III, 18 Type IV, and 5 Type V). The specimens, which had been embedded in polymethylmethacrylate (PMMA), were micromilled and carbon coated to permit backscattered electron imaging. Reference biopsies from very young children often contained densely mineralized cartilage, and evidence of rapid cortical drift. Circumferential lamellae became a prominent feature after the toddler stage, and active remodeling and slower cortical drift continued through childhood. The biopsies from older teenagers and young adults were indistinguishable. Occasional mineralized osteocyte lacunae were detected in even the youngest children. Bone from children with OI Type I often appeared normal in microstructure and amount, but in some there was a dearth of bone and an abundance of osteocytes. Compared with age-matched controls, cortical and trabecular bone from children with OI Types III and IV were markedly sparse and very cellular, and primary osteonal systems continued to be formed later than expected. A distinguishing feature of the bone from OI Type V patients was the failure of patches of bone to mineralize, especially adjoining a reversal line. Packets of bone tissue exhibiting either considerably higher than normal or deficient mineralization would contribute to the characteristic trait of mechanical weakness.

Adolescent↗

PubMed1999

The mineralization density of iliac crest bone from children with osteogenesis imperfecta.

We studied iliac crest biopsy cores taken from young individuals with osteogenesis imperfecta of several types, and from age-matched normals; the same samples had been used in prior studies using conventional light microscopic histomorphometric procedures. The PMMA blocks were micro-milled to a fine finish, carbon coated, and imaged using backscattered electrons (BSE) in an automated digital scanning electron microscope (SEM). For comparison of BSE signal levels between samples, microscope operation parameters were standardized by reference to halogenated dimethacrylate standards, and recording data from stereological arrays of 512*512 nonoverlapping pixels at 3.5 micrometer separation. All OI types showed higher average mineralization densities than age- and site-matched normals. This is interpreted as the result of the failure in matrix assembly, such that it has a higher water volume fraction available for mineral deposition. Added to the net deficit in bone quantity, the predicted higher stiffness of the more mineralized bone will account for much of the observed 'brittleness' that characterizes this class of genetic disease. The mean mineralization density, which was higher in types III, IV, and V than in type I, appears to be correlated with disease severity.

Adolescent↗

PubMed1999

The resorption of vital and devitalized bone in vitro: significance for bone grafts.

Several studies have suggested that devitalized bone is less satisfactory than live tissue for surgical grafting purposes because an initial resorption step, prior to new formation, is lacking. We have compared the osteoclastic resorption of cultured bone containing living osteocytes with that of similar bone in which the osteocytes were dead. In experiment I, transverse slices cut from freshly harvested adult rabbit femora were either placed in phosphate buffered saline (Set 1) or subjected to freezing and thawing (Set 2). In experiment II, a heated set (Set 3) was prepared in addition. All slices were cultured with osteoclasts for 24 hours, eight slices per set being seeded with bone cells in experiment I and three per set in experiment II. The areas and volumes of resorption pits formed during the culture period were measured using reflection confocal microscopy. In both experiments, the mean values for the areas of the pits were smaller in the bone containing live osteocytes (P < 0.03, Mann Whitney test), and in experiment II the volumes of the pits in Set 1 were smaller than those in Set 3 (P < 0. 0001, Mann Whitney test). However, in neither experiment was there a significant difference between the Sets in the volume:area ratios (mean depths) of the pits. The findings show that devitalized bone is resorbed by osteoclasts at least as readily as bone containing vital osteocytes in vitro, and indicate that if grafted devitalized bone resorbs less well in vivo it is not because the bone tissue is intrinsically resistant to osteoclastic resorption.

Animals↗

PubMed1999

Osteoconduction in large macroporous hydroxyapatite ceramic implants: evidence for a complementary integration and disintegration mechanism.

Large, cylindrical implants of a porous calcium phosphate ceramic ("hydroxyapatite" starting material, HAC) were used to replace far greater than critical-sized sections of the midshaft of sheep tibiae and retrieved at 2 and 9 months; external fixation was used in the first 5 months. Excellent clinical function of these implants was reported in a previous study. The material retrieved was embedded in PMMA, and blocks were sectioned and surfaces were polished and carbon coated prior to study using digital backscattered electron (BSE) imaging. Detailed scanning electron microscopy study of the pattern of osseointegration of the implanted material at early (2 months) and late (9 months) timepoints revealed a previously unrecognized pattern of integration/disintegration of this implant material in tandem with bone growth. We conclude that bone adaptation to the HAC leads to its fracture and that the newly generated surfaces are equally osteoconductive. This leads to a self-propagating, self-annealing system in which defects in the HAC are mended by intercalation of bone.

Animals↗

PubMed1999

Three dimensional structure of the distal condyles of the third metacarpal bone of the horse.

This study examined the three-dimensional (3D) microarchitecture of regions of the equine third metacarpal bone (McIII) commonly involved in distal condylar fractures. Limbs were obtained from Thoroughbred horses (neonates to age 24 years) destroyed for inoperable fractures and a variety of other conditions. Beams, blocks and sections were cut in the principal axes, some embedded in PMMA and others examined unembedded. Several methods were used to study the 3D structure, including conventional and confocal optical microscopy, scanning electron microscopy (SEM) and radiography. The mineralised articular cartilage tends to cleave in the sagittal plane. Proximal to the subchondral bone, the main trabeculae are robust plates running in the sagittal direction with less significant mediolateral connections. Small blood vessel canals lie inside the sagittal plates. This structure gives maximum strength and protection in the sagittal plane in which the bone rotates, but offers minimal resistance to fracture propagation in this plane. The anatomical course of the common distal condylar fractures of the third metacarpal bones can be explained by underlying anisotropic structural features of the mineralised tissues.

Animals↗

PubMed1999

Structural variation of the distal condyles of the third metacarpal and third metatarsal bones in the horse.

This study examined 3-dimensional (3D) distribution of sectors with contrasting density in the equine third metacarpal (McIII) and third metatarsal (MtIII) bones with a view to explaining the aetiology of distal condylar fractures. Macroradiography and computed tomographic (CT) imaging were used in the nondestructive study of bones obtained from horses, most of which were Thoroughbreds in race training. Distal condylar regions of McIII and MtIII were also studied in microradiographs of 100 microm thick mediolateral sections cut perpendicular to the dorsal and palmar/plantar articular surfaces. Qualitative and quantitative results from all methods used (radiography, CT and microradiographic stereology) demonstrated a densification (sclerosis) of subchondral bone located in the palmar/plantar regions of the medial and lateral condyles of both McIII and MtIII. Substantial density gradients between the denser condyles and the subchondral bone of the sagittal groove were shown to equate with anatomical differences in loading intensity during locomotion. It is hypothesised that such differences in bone density results in stress concentration at the palmar/plantar aspect of the condylar grooves, which may predispose to fracture.

Animals↗

PubMed1999

Pathology of the distal condyles of the third metacarpal and third metatarsal bones of the horse.

This study examined material from Thoroughbred horses, the majority of which had been in race training, for evidence of pathology in the third metacarpal (McIII) and third metatarsal (MtIII) bones which might be related to the occurrence of distal condylar fractures. Whole bone samples were studied and documented by macrophotography prior to macroradiography and computed tomographic (CT) imaging. Microradiographs were made from 100 microm thick mediolateral sections cut perpendicular to the dorsal and palmar/plantar articular surfaces of distal condylar regions of McIII and MtIII. Blocks were prepared for morphological imaging using the backscattered electron mode of scanning electron microscopy (BSE SEM). Linear defects in mineralised articular cartilage and subchondral bone were found in the palmar/plantar aspects of the condylar grooves adjacent to the sagittal ridge. These were closely related to the pattern of densification of the subchondral bone and were associated with intense focal remodelling of the immediately adjacent and subjacent bone. Parasagittal fractures of the condyles originated in similar defects. A unifying hypothesis for the aetiopathogenesis of these fractures is presented.

Animals↗

PubMed1999

Effect of exercise on bone density in distal regions of the equine third metacarpal bone in 2-year-old thoroughbreds.

The present study addressed the question of whether training induces changes in bone density in the younger racehorse in regions relevant to the genesis of the common sagittal condylar fracture pattern and, if so, the nature of such alteration. Third metacarpal bones (McIII) were obtained from 12 experimental Thoroughbred, unbroken fillies, age 18.1-21.0 months at entry to the study. Six (Group E) undertook 19 weeks of progressive high intensity exercise on a high-speed treadmill at 3% incline. Six (Group C) walked 40 min each day. Clinical bone density was studied by Computed Tomography (CT) of the right McIII. 1:1 aspects of bone density were studied by digital radiography of slices and microscopic aspects by backscattered electron (BSE) imaging. There was a distinct pattern of regional variation in bone density throughout the distal condyles of McIII. Bone density was greater in specimens from Group E than those from Group C by CT, by radiographic density and by bone volume fraction as determined from backscattered electron images: the latter also showed that the most important change was in the increased amount of bone deposited within antecedent marrow space in cancellous tissue in Group E compared with Group C, with more extensive regional involvement in the highly loaded (distopalmar) aspects of the medial and lateral condyles. However, this space-filling bone fraction had a lower degree of mineralisation than the prior bone tissue, showing that CT and radiography underestimate the resultant increased bone volume fraction. Stress fractures of the distal condyles of the McIII are common in Thoroughbred racehorses. We propose that excess stiffening within the condyles due to extensive new bone formation may lead to concentration of strain at the condylar grooves and incipient cracking through calcified cartilage and into the subchondral bone.

Animals↗

PubMed1998

Impaired osteoclastic bone resorption leads to osteopetrosis in cathepsin-K-deficient mice.

Cathepsin K is a recently identified lysosomal cysteine proteinase. It is abundant in osteoclasts, where it is believed to play a vital role in the resorption and remodeling of bone. Pycnodysostosis is a rare inherited osteochondrodysplasia that is caused by mutations of the cathepsin-K gene, characterized by osteosclerosis, short stature, and acroosteolysis of the distal phalanges. With a view to delineating the role of cathepsin K in bone resorption, we generated mice with a targeted disruption of this proteinase. Cathepsin-K-deficient mice survive and are fertile, but display an osteopetrotic phenotype with excessive trabeculation of the bone-marrow space. Cathepsin-K-deficient osteoclasts manifested a modified ultrastructural appearance: their resorptive surface was poorly defined with a broad demineralized matrix fringe containing undigested fine collagen fibrils; their ruffled borders lacked crystal-like inclusions, and they were devoid of collagen-fibril-containing cytoplasmic vacuoles. Assaying the resorptive activity of cathepsin-K-deficient osteoclasts in vitro revealed this function to be severely impaired, which supports the contention that cathepsin K is of major importance in bone remodeling.

Animals↗

PubMed1998

Bone and BSE.

Explore the source record for details and available documents.

Animals↗

PubMed1998

Monte Carlo simulation of electron backscattering from compounds with low mean atomic number.

This paper reports a Monte Carlo simulation where a single atom scattering model is adopted. The element taking part in each electron-atom interaction is selected on the basis of its contribution either to the total elastic cross section or to the electron's mean free path. Both Rutherford and Mott scattering are considered, with the continuous slowing down process of Bethe used to calculate the energy loss to the system. The backscattered electron coefficients show good agreement with experimental results from a large group of low atomic number materials when using a model which selects the scattering atom by its contribution to the whole compound calculated from its atomic fraction of the total elastic cross-section.

Computer Simulation↗

PubMed1998

Effect of estrogen suppression on the mineralization density of iliac crest biopsies in young women as assessed by backscattered electron imaging.

The effects of estrogen suppression on bone mineralization in young women were studied by quantitative backscattered electron (BSE) imaging of transiliac biopsies taken before and after treatment for endometriosis. Treatment (6 months) was with analogs of gonadotrophin releasing hormone (GnRH) given either alone (six paired biopsies), which resulted in a marked reduction in the levels of circulating estrogen, or in conjunction with tibolone, a synthetic steroid with estrogenic, progestrogenic, and androgenic properties (four paired biopsies). Estrogen withdrawal increased (p < 0.01) and concomitant tibolone treatment decreased (p < 0.05) the overall mean bone density. Estrogen withdrawal increased the fraction of bone with a high mineralization density [pretreatment: 0.236+/-0.007; GnRH: 0.279+/-0.009, mean +/- standard error of the mean (SEM); p < 0.01]. The concomitant addition of tibolone reversed these effects and increased the proportion of bone with a low mineralization density (pretreatment: 0.198 +/- 0.005; tibolone: 0.230 +/-0.008, p < 0.01). Using previously published data, the mean bone density was inversely correlated with mean wall thickness in cancellous bone (p = 0.030) and with the percentage of active osteons (p = 0.023) in cortical bone. Although treatment had similar effects on the mean bone mineralization density of cortical and cancellous bone, there were different distributions of mineralization between the two sites, with cancellous bone having more skewed and kurtotic distributions both before and after estrogen withdrawal. This study indicates that a short-term estrogen suppression results in the accumulation of bone with a higher mineralization density. As bone with a high mineral content has a decreased impact resistance, this might increase fracture risk. Understanding the cellular and biochemical mechanisms responsible for the local distribution of bone mineral when estrogen is withdrawn may allow the development of new strategies for maintaining bone quality after menopause.

Adult↗

PubMed1998

Variation in the apparent density of human mandibular bone with age and dental status.

This study examines the variability in the anatomy of mandibles of differing ages and different stages of tooth loss. Mandibles from individuals between 19 and 96 y were sectioned into 2 mm thick vertical plane-parallel slices and cleaned of marrow and periosteum. The apparent density (mass per unit volume in g/ml) from midline (MID) and mental foramen region (MF) sites was determined by weighing the slices and dividing by a volume calculated as the product of section thickness and the mean area of the 2 sides of the section. The cortical thickness of the inferior border and the basal and alveolar bone heights were measured in radiographs of the slices. Mandibular apparent density was negatively correlated with the cross sectional area (midline r=-0.48, mental foramen r=-0.45), and at the midline was significantly greater in edentulous than in dentate individuals (means (+/-S.E.M.) edentulous n=13: 1.43 (+/-0.07) g/ml; dentate n=17: 1.27 (+/-0.04) g/ml, P < 0.05). Where a large enough age range was available, mandibular apparent bone density showed a significant increase with age (midline males: r=0.53, n=18) especially for dentate individuals (r=0.91, n=8). There was a correlation between the apparent densities at the two sites in the same mandible (r=0.64), with the values obtained for the midline being significantly greater than for the mental foramen region (midline 1.34 (+/-0.04) g/ml; mental foramen 1.19 (+/-0.04) g/ml, P < 0.001, paired t test). The mandible shows great interindividual variability, but there may be a considerable reduction in cross sectional girth of the mandible following tooth loss, and, unlike postcranial sites, an increase in apparent density with age.

Adult↗

PubMed1998

Mineralisation density of human mandibular bone: quantitative backscattered electron image analysis.

This study examined the tissue level mineralisation density distribution in mandibles from 88 adult humans. Mandibles (19-96 y) were sectioned vertically in midline (MID), mental foramen (MF), and third molar (M3) regions. Surgical fragments from M3 were obtained from individuals aged 16-38 y. All specimens were cleaned, embedded in PMMA, micromilled and examined by digital 20 kV backscattered electron (BSE) stereology. Quantitation was based on rescaling image histograms to the signal range between a monobrominated (0) and a monoiodinated (255) dimethacrylate resin standard. Mineralisation density increased with age (r=0.70; P < 0.0001): the mean for 39 individuals aged between 16 and 50 y was significantly lower (P < 0.0001) than for 35 individuals over 51 y (mean (+/-S.E.M.): 158.20 (1.63) and 174.71 (1.27) normalised grey level units respectively). There was good correlation in mean mineralisation density between different sites in the same mandible, but MID was significantly less highly mineralised than the other sites: MID 173.90, MF 177.34, M3 177.11 (P < 0.002 and 0.01 for MF and M3 respectively; paired t test), as was the alveolar bone density when compared with the bone of the inferior cortex (e.g. MID: 171.13 (1.53) and 174.46 (1.14) P < 0.0001). No sex difference was found. Partially dentate mandibles generally had regions of higher mineralisation than fully dentate and edentulous mandibles. The lowest density bone occurred at the alveolar crest anteriorly and superolingually at M3, matching sites of net resorption following tooth loss. Highest densities were found inferolingually at MID, inferiorly at MF and buccally at M3, matching the sites thought to experience the highest functional strains. This stresses the importance that local factors may have in the remodelling of the edentulous mandible. Morphology showed that there is a preponderance of highly mineralised cement lines, and of packets containing dead, mineralised, osteocytes.

Adolescent↗