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PubMed1988

Flurbiprofen-induced stimulation of periosteal bone formation and inhibition of bone resorption in older rats.

The skeletal effects of flurbiprofen (Fb), a nonsteroidal anti-inflammatory drug, was studied by histomorphometry in 9-month-old retired female breeder, Sprague-Dawley rats. Flurbiprofen was given subcutaneously at 0, 0.2, 0.1, 0.5, 2.5, or 5 mg/kg/d for 21 days. Flurbiprofen had no effect on longitudinal growth, but stimulated radial growth (+200%) over controls. In the tibial shaft, Fb stimulated the mineral apposition rate (+25%), mineral bone formation rate (+100%), and periosteal labeling length (+64%) at the 2.5 and 5.0 mg Fb/kg dose levels, and had no effect on marrow cavity size compared to controls. However, these changes were insufficient to increase cortical bone mass. In the proximal tibial metaphysis, Fb suppressed osteoclasts/mm2 of metaphyseal tissue (-47%), osteoclasts/mm of bone surface (-46%), and the osteoclast/osteoblast ratio (-50%), increased the calcified cartilage core population (+100%), and had no effect on osteoblast numbers at all dose levels. There was an insignificant increase in metaphyseal cancellous bone mass. The current study leads to the conclusion that flurbiprofen-stimulated periosteal bone growth was due to direct stimulation of osteoblast recruitment and activity independent of longitudinal bone growth. Further, it confirms early findings in young rats that flurbiprofen induced depressed bone resorption without lowering bone formation. However, because of insufficient treatment time, the older rat did not accumulate bone as the young rats did.

Age Factors↗
PubMed1988

Skeletal tissue responses to thermal injury: an experimental study.

Skeletal changes occurring secondary to burn injuries were studied in an experimental animal model for thermal injury. One hindlimb of female Sprague-Dawley rats (200-250g) was subjected to a standardized thermal injury; the other hindlimb was left untreated. Control animals received no experimental treatment. Effects on skeletal architecture were studied at the proximal tibial metaphysis and tibial diaphysis using static histomorphometry. Bone formation dynamics were studied from a series of bone fluorochrome labels administered before the experiment began, early (days 8, 9) postburn treatment (PBT) and late PBT (days 17, 18). Animals were sacrificed on day 21 PBT. In proximal tibial metaphyses of burn-treated limbs, trabecular bone area (TBA) and trabecular number in all regions except the primary spongiosa, were significantly reduced. TBA was also decreased, but not significantly in nontreated limbs. Longitudinal growth rate, growth plate thickness and growth cartilage cell production rate are greater in burn-treated than in nonburned and control bones. Burn-treated diaphyses showed extensive woven bone formation at periosteal surfaces, and corresponding increases of bone areas and periosteal perimeters. Endocortical surfaces showed only typical occasional resorption areas. No intracortical changes were observed. Mineral appositional rate (MAR) and bone formation rate (BFR) at endocortical surfaces were markedly depressed after thermal injury, significant changes were noted in both limbs of treated animals. Among burned limbs, the early PBT label was absent from all specimens, indicating a virtual shutdown of osteoblast activity and recruitment. Similarly in nonburned limb bone, the label was absent from 50% of the specimens; in those bones in which the label was present, label lengths, appositional and bone formation rates were significantly reduced relative to the control specimens. Comparison of average bone formation dynamics for the total PBT interval indicates that MAR and BFR in burned treated tibiae were reduced to approximately 25% of control values. MAR and BFR from the nonburned side of treated animals were significantly reduced as well, to about 55% of control values. These data indicate that the principal metaphyseal effects of thermal injury are stimulation of growth cartilage proliferation, and depression of ossification and osteoblast activity. In diaphyses, thermal injury causes extensive local periosteal woven bone proliferation and a dramatic depression of endosteal bone formation. The latter effect, while more severe locally, is also evident systemically.

Animals↗
PubMed1991

Dynamic histomorphometric evaluation of human fetal bone formation.

We have evaluated dynamic and static parameters of bone formation in femoral metaphyses collected from two human fetuses at 19 weeks of gestation. Tetracycline was administered to the mother at set intervals (2-5-2 day schedule) before interruption of pregnancy. Labels were distinct and sharply linear, suggesting a well organized calcification front at this early stage of mineralization. Mineral apposition rate (MAR) was fastest (4.1 +/- 0.3 microns/d) in the periosteal (Ps) envelope, and about half that value in the endosteal envelopes (endocortical: 2.5 +/- 0.1, cancellous 2.1 +/- 0.1 microns/d). Because cellular activities may vary throughout the metaphyseal area, sections were arbitrarily separated in 0.75 mm layers starting from the growth plate. Three measured parameters decreased rapidly with increasing distance from the physis: Ps MAR: 4.9 to 2.3 microns/d, trabecular osteoid thickness: 5.9 to 1.2 microns, and cartilage volume (CgV/TV): 5.4% to 1.2%. Others did not vary significantly along the metaphysis. Comparison of several static parameters with those measured in five autopsy specimens from full-term infants showed that bone and cartilage volume, and trabecular thickness increased while osteoid thickness and parameters of resorption decreased in the second half of the gestation period. The study indicates that fetal bone matrix mineralization is already highly organized at mid-gestation, and validates the use of histomorphometry to assess bone maturation during early skeletal development.

Bone Development↗
PubMed1995

Effects of basic fibroblast growth factor (bFGF) on bone formation in growing rats.

The effects of basic fibroblasts growth factor (bFGF) administered intravenously at dosages of 0.1 and 0.3 mg/kg per day for 7 days to growing rats are reported. Static and dynamic histomorphometry techniques were applied to the microradiographs and undecalcified ground sections of the proximal tibiae and tibial shafts. The bone histomorphometric analyses in the proximal tibia revealed that 0.1 mg/kg per day of bFGF increased longitudinal growth rate, cartilage cell production rate, and metaphyseal bone area. In the tibial shaft, the endocortical mineral apposition and bone formation rates, total bone area, total osteoid area, and medullary bone area were increased, but the periosteal mineral apposition and bone formation rates were depressed. Two weeks after the cessation of treatment, the increased osteoid bone on the endocortical surface and in the marrow cavity was completely calcified, and the total mineralized area in the tibial shaft was significantly increased. The rats given 0.3 mg of bFGF/kg per day showed retarded weight gain, defective calcification at the growth plate metaphyseal junction, and on the endocortical surface. The growth plate width was increased, and the longitudinal growth rate, cartilage cell production rate, endocortical labeled surface, and bone formation rate were decreased. Two weeks after the cessation of treatment, these changes were almost reversed, and the longitudinal growth rate and cartilage cell production rate were increased as rebound phenomena. These results suggest that a low dose (0.1 mg/kg per day) of bFGF stimulates endosteal and endochondral bone formation and depresses periosteal bone formation in growing rats.

Analysis of Variance↗
PubMed1995

Remobilization partially restored the bone mass in a non-growing cancellous bone site following long term immobilization.

There is no report in the rat of the effects of remobilization (RM) in an adult bone site. The aim of this study was to determine whether complete recovery from IM-induced bone loss will occur in a non-growing bone site, the distal tibia. Seventy-five 6-month-old virgin Sprague-Dawley female rats were used in this study. Their hindlimbs were immobilized against the abdomen with bandages for 18 weeks, then remobilized for 2, 10 or 20 weeks. Distal tibial sections were analyzed in the former epiphysis, 0.3 mm proximal from the calcified cartilage, and in trabecular bone of the former metaphysis between 0.3 mm and 1.92 mm proximal to the former epiphysis. A significant bone loss occurred in both former epiphyseal and metaphyseal trabeculae at 18 weeks after IM. The lost bone was partially recovered at 10 weeks of RM, but the bone mass was still lower than in aging controls by the end of the study. The partial recovery was characterized by decreasing former epiphyseal bone porosity and thickening of former metaphyseal trabeculae with no effect on trabecular number. We concluded that both distal tibia regions only partially recovered, during 20 weeks of RM from the long time IM.

Animals↗
PubMed1995

Canine bone marrow cell cultures infected with canine distemper virus: an in vitro model of Paget's disease.

We have previously shown that the canine paramyxovirus, canine distemper virus (CDV), is a possible aetiologic agent in Paget's disease of bone and in the canine bone disorder, metaphyseal osteopathy. More recently, we have examined the effects of CDV on the formation of multinucleated, tartrate resistant acid phosphatase positive, calcitonin receptor positive, osteoclast-like cells in cultures of canine bone marrow mononuclear cells, and shown that both in vitro and in vivo infection with CDV produced a dose dependent increase in the number and size of osteoclast-like cells. We have now extended these results to show that CDV infection induces interleukin-6 and c-Fos mRNA in these cells, similar to our recent findings in pagetic bone cells. These results further support the hypothesis that CDV might be involved in the aetiopathogenesis of Paget's disease and metaphyseal osteopathy and suggest that canine marrow culture systems will prove useful as an in vitro model to examine the disease processes in more detail.

Animals↗
PubMed1995

Comparison of the effects of intermittent and continuous administration of human parathyroid hormone(1-34) on rat bone.

We compared the effects of synthetic human parathyroid hormone (1-34) (hPTH[1-34]) on rat bones when administered by intermittent injection and by continuous infusion for 4 weeks. Continuous infusion of hPTH(1-34) caused a dose-dependent decrease in the dry weight of the femur and a hyperparathyroidism-like condition in the high-dose group (214 ng/kg/h). In this group, although bone morphology was quite abnormal, the metaphyseal trabecular bone volume increased, whereas the epiphyseal trabecular bone volume tended to decrease, enhancing both bone resorption and formation. The diaphyseal cortical bone of the tibia became markedly porous, and this appeared to be the main cause of the decrease in total bone weight. Conversely, the dry weight of the femur increased in a dose-dependent manner in the intermittent-injection groups. Neither porosity of the cortical bone nor abnormal morphology of the trabecular bone was observed. The volume of the metaphyseal trabecular bone increased while retaining its normal morphology. The epiphyseal trabecular bone formation obviously increased without increase in the number of osteoclasts. In other words, it was postulated that the total weight of bone increased because intermittent injection of hPTH(1-34) increased the trabecular bone volume without loss of the cortical bone volume. These results show that either mode of treatment with hPTH(1-34) continuously accelerated bone formation, whereas the continuous infusion was essential for persistently and markedly enhanced acceleration of bone resorption. It appears that the increase in bone volume with intermittent injection of hPTH(1-34) resulted from the prominent manifestation of its bone-formative action rather than from its bone-resorptive action.(ABSTRACT TRUNCATED AT 250 WORDS)

Alkaline Phosphatase↗
PubMed1996

Influence of vitamin D status on hyaluronan localization in bone.

The distribution of hyaluronan was investigated in the proximal tibiotarsal bones of normal (vitamin D-treated) chicks, and chicks with rachitic lesions induced by vitamin D deficiency. Localization studies using a biotinylated hyaluronan-binding probe revealed that in vitamin D-treated chicks, a high level of hyaluronan staining was present in upper proliferative zone cartilage and upper hypertrophic zone cartilage. Hyaluronan staining was greatly reduced in the zone of provisional calcification. In the metaphyses and diaphyses of normal chicks hyaluronan was predominantly localized to the non-bone-forming surfaces of osteoblasts but was also present on the basolateral surfaces of lining cells and osteoclasts. Marked changes in hyaluronan distribution were observed in vitamin D-deficient chicks. The amount of hyaluronan present in proliferative zone growth cartilage was similar to control chicks, although with a more widespread distribution, extending into lower proliferative zone cartilage. In the zone of hypertrophy/calcification, biochemical analyses revealed that hyaluronan levels in rachitic chicks were about 3.6 times greater than in vitamin D-treated chicks; localization studies demonstrated that this increase was associated with the presence of hyaluronan-positive spindle-shaped cells in the metaphyseal vascular spaces. Intense hyaluronan staining was also associated with abundant spindle-shaped cells occupying the marrow spaces of rachitic diaphyseal bone. The distribution of hyaluronan in vitamin D-treated chick bone, and the alterations observed in rachitic tissue suggests a role for hyaluronan in endochondral bone formation.

Animals↗
PubMed1996

Combined use of malachite green fixation and PLA2-gold complex technique to localize phospholipids in areas of early calcification of rat epiphyseal cartilage and bone.

Two cytochemical methods (malachite green fixation and PLA2-gold complex technique) were combined in order to detect the presence and ultrastructural distribution of phospholipids in epiphyseal cartilage and metaphyseal bone of 25-day-old rats. Chondrocytes and osteoblasts showed a more intense PLA2-gold complex labeling of rough endoplasmic reticulum than mitochondria and plasma membranes. Roundish osmiophilic, electron-dense, lightly labeled structures were visible at the periphery of the cells. In areas of early mineralization of cartilage, not all the matrix vesicles were labeled by PLA2-gold complex. Calcification nodules showed intense labeling in comparison with the surrounding, lightly labeled uncalcified matrix; gold particles were chiefly found at their periphery. Calcification nodules of metaphyseal bone were deeply electron-dense after glutaraldehyde-malachite green fixation; PLA2-gold labeling was mainly found in connection with crystals, whereas the uncalcified matrix was weakly labeled. Calcified bone matrix showed a heavy labeling with randomly scattered gold particles. When pre-embedding decalcification was carried out in the presence of malachite green, a good preservation of organic component was obtained. The PLA2-gold positivity of decalcified areas of cartilage and bone confirmed the presence of phospholipids in mineralized matrix.

Animals↗
PubMed2005

Differential effects of alendronate treatment on bone from growing osteogenesis imperfecta and wild-type mouse.

Bisphosphonates have been reported to decrease the number of fractures in children with osteogenesis imperfecta (OI). The current study sought to further explore bisphosphonate-associated bone changes in OI by investigating the effects of alendronate (ALN) treatment on bone mechanical and material properties in osteogenesis imperfecta (oim/oim) and wild-type (+/+) mice treated with 26-73 microg kg(-1) day(-1) of ALN for 8 weeks via subcutaneously implanted pumps. Femoral three-point bend tests to evaluate cortical bone were combined with geometric and material density analysis. Cortical and trabecular architecture of metaphyseal bone were histomorphometrically evaluated and material density assessed by quantitative backscattered electron imaging (qBEI). For the cortical oim/oim bone, which revealed principally inferior biomechanical properties compared to +/+ bone, ALN neither improved cortical strength or any other mechanical property, nor affected cortical width (Ct.Wi.) or material density. In contrast, for the +/+ mice, bone strength was enhanced (+22%, P < 0.05) though coupled with increased brittleness (+28%, P < 0.05). This mechanical improvement was associated with an increase in Ct.Wi. (+17.3%, P = 0.02) and a reduction in heterogeneity of cortical mineralization (Ca(Width), -4%, P = 0.04). In the metaphysis, ALN raised cancellous bone volume (BV/TV) significantly in oim/oim as well as in +/+ mice (+97%, P = 0.008 and +200%, P < 0.0001, respectively). This occurred without any change in either material density or trabecular thickness (Tb.Th.) in the oim/oim mice, while in the +/+ mice, material density increased slightly but significantly (+3%, P = 0.004), and Tb.Th. increased by 77% (P < 0.0001). Taken together, these results illustrate the differential effects of ALN on oim/oim vs. +/+ bone, as well as on specific skeletal sites, i.e., cortical vs. trabecular bone. ALN augmented the mechanical, geometrical, and material properties of +/+ cortical and trabecular bone, while the only observable improvement to the oim/oim bone was increased cancellous bone volume. This suggests that in this mouse model of OI, the previously demonstrated bisphosphonate-associated reduction in fractures is primarily attributable to increased metaphyseal bone mass.

Alendronate↗
PubMed2006

Which radiological investigations should be performed to identify fractures in suspected child abuse?

AIMS: To determine which radiological investigations should be performed and which children should be investigated. MATERIALS AND METHODS: An all language literature search of original articles; from 1950-October 2005. Two reviewers independently reviewed each article. A third was carried out on disagreement. Each study was assessed using standardised data extraction, critical appraisal and evidence forms. RESULTS: Thirty-four studies were included. Fifteen addressed the question: which investigation has a higher yield, skeletal surveys (SS) or bone scintigraphy (BS)? Studies gave conflicting results. Overall neither investigation is as good as the two combined. BS predominately missed skull, metaphyseal and epiphyseal fractures, whereas SS commonly missed rib fractures. Two studies showed that a repeat SS 2 weeks after the initial study provided significant additional information about tentative findings, the number and age of fractures. A comparative study evaluated additional oblique views of ribs in 73 children and showed improved diagnostic sensitivity, specificity and accuracy. Four studies addressed the diagnostic yield for occult fractures with respect to age. This was significant for children under 2-years old. CONCLUSIONS: In children under 2-years old, where physical abuse is suspected, diagnostic imaging of the skeleton should be mandatory. SS or BS alone is inadequate to identify all fractures. It is recommended that all SS should include oblique views of the ribs. This review suggests that the following options would optimize the diagnostic yield. However, each needs to be evaluated prospectively: SS that includes oblique views, SS and BS, a SS with repeat SS or selected images 2 weeks later or a BS plus skull radiography and coned views of metaphyses and epiphyses.

Adolescent↗
PubMed2003

The LCP-concept in the operative treatment of distal humerus fractures--biological, biomechanical and surgical aspects.

Distal humerus fractures in adults are treated by open reduction and internal fixation, which produces good results in the majority of patients. However, in elderly patients or in cases with metaphyseal comminution, stable fracture fixation still remains problematic. Anatomical joint reconstruction and primary stable osteosynthesis are often particularly difficult to achieve in this group of patients since poor bone mineral quality is frequently encountered. Consequently, longer immobilization is necessary, which is known to negatively influence functional outcome. Over the past few years, double-plate osteosynthesis techniques using different configurations have become the treatment of choice. Nevertheless, complications due to inappropriate primary stability and/or implant failure have been described. Investigations on whether the recently introduced Locking Compression Plates (LCPs) could enhance primary stability are rare. On the basis of clinical and biomechanical experiences, the authors consider LCPs a helpful tool for increasing primary stability in osteosynthesis of distal humerus fractures. LCPs might be of substantial advantage in patients with diminished bone mineral quality or in the presence of metaphyseal comminution.

Aged↗
PubMed2005

Subject-specific finite element models of long bones: An in vitro evaluation of the overall accuracy.

The determination of the mechanical stresses induced in human bones is of great importance in both research and clinical practice. Since the stresses in bones cannot be measured non-invasively in vivo, the only way to estimate them is through subject-specific finite element modelling. Several methods exist for the automatic generation of these models from CT data, but before bringing them in the clinical practice it is necessary to assess their accuracy in the predictions of the bone stresses. Particular attention should be paid to those regions, like the epiphyseal and metaphyseal parts of long bones, where the automatic methods are typically less accurate. Aim of the present study was to implement a general procedure to automatically generate subject-specific finite element models of bones from CT data and estimate the accuracy of this general procedure by applying it to one real femur. This femur was tested in vitro under five different loading scenarios and the results of these tests were used to verify how the adoption of a simplified two-material homogeneous model would change the accuracy with respect to the density-based inhomogeneous one, with special attention paid to the epiphyseal and metaphyseal proximal regions of the bone. The results showed that the density-based inhomogeneous model predicts with a very good accuracy the measured stresses (R(2)=0.91, RMSE=8.6%, peak error=27%), while the two-material model was less accurate (R(2)=0.89, RMSE=9.6%, peak error=35%). The results showed that it is possible to automatically generate accurate finite element models of bones from CT data and that the strategy of material properties mapping has a significant influence on its accuracy.

Femur↗
PubMed2006

Why fine-wire fixators work: an analysis of pressure distribution at the wire-bone interface.

Tensioned fine-wire external fixator systems have been used successfully for the treatment of fractures, mal-unions and for limb lengthening for many years. When used in metaphyseal bone, this type of fixator has a lower loosening rate than half-pin fixators. The differing mechanical properties of these fixator systems have been investigated extensively; however, most studies have centered on the mechanical properties of the fixator as a whole. Our knowledge of the interactions occurring at the interface between implant and bone remains sparse. In order to investigate this interaction, we devised a simple experimental model to characterise the distribution of pressure in cancellous bone surrounding a tensioned wire under loading conditions. Comparison was then made to a similar model of a half-pin fixator. Pressure was measured using pressure sensitive film at various distances away from the implant-bone interface. Static, single cycle loading of the model was performed with a Universal Testing Machine. Pressure distribution in the fine-wire model was found to occur in three regions: polar, beam loading and uniform. Polar patterns were seen closest to the wire with pressure concentrated at the entry and exit points of the wire. Beam loading was seen at a distance of 1.5 mm from the wire and pressure reached a uniform distribution at 4.0 mm. Most of the pressure measured was less than 2 MPa, which is less than the yield strength of cancellous bone (2-7 MPa). Higher loads produced higher stresses but the distribution pattern was similar. In contrast, the half-pin model showed far higher pressures (20 MPa), which were present deeper in the bone specimen. These results further our understanding of the biomechanics of fine-wire fixators and may explain the lower loosening rate of this type of fixator when compared to half-pin fixators used in metaphyseal bone.

Biomechanical Phenomena↗
PubMed2005

Preventive effect of Abelmoschus manihot (L.) Medik. on bone loss in the ovariectomised rats.

Because the biggest culprit in pathogenesis of osteoporosis is oestrogen deficiency, hormone replacement therapy remained the mainstay for prevention. However most of postmenopausal women are more inclined to use natural alternative. We thus investigated the ability of Abelmoschus manihot, a herbal medicine to prevent bone loss in ovariectomised rats. Female Wistar rats were sham operated (SH: 8) or ovariectomised (OVX: 24). On day 0, OVX rats were randomly assigned to groups as follows: eight received 10% Abelmoschus manihot leaves in their diet, eight were given 15% Abelmoschus manihot leaves and eight were untreated (OVX). Compounds were mixed with a soy protein-free diet and given orally for 3 months. At necropsy, bone mineral density (BMD) in the femur and in its metaphyseal zone was lower in OVX than SH (p<0.05). This osteopenia was prevented by consumption of the highest dose of Abelmoschus manihot leaves. Bone mineral content (BMC) in the total femur and its metaphyseal and diaphyseal subregions was improved, as well (p<0.05). This could be explained by a trend towards decreased bone resorption. The lowest dose did not elicit any significant effect. In conclusion, Abelmoschus manihot consumption, at the dose of 15% in the diet, provided bone-sparing effects by improving both BMD and BMC.

Abelmoschus↗
PubMedDate not supplied

Predictors of humeral head ischemia after intracapsular fracture of the proximal humerus.

The purpose of this study was to evaluate predictors of fracture-induced humeral head ischemia. Between February 1998 and December 2001, 100 intracapsular fractures of the proximal humerus, treated by open surgery, were included in a prospective surgical evaluation protocol (mean age, 60 years; minimum, 21 years; maximum, 88 years; 45 men; 57 right shoulders). Fracture morphology was assessed following a structured questionnaire and based on radiographic and intraoperative findings. Perfusion was assessed intraoperatively by observation of backflow after a borehole was drilled into the central part of the head in all shoulders and by intraosseous laser Doppler flowmetry in 46. Good predictors of ischemia were the length of the metaphyseal head extension (accuracy, 0.84 for calcar segments <8 mm), the integrity of the medial hinge (accuracy, 0.79 for disrupted hinge), and the basic fracture pattern (accuracy, 0.7 for combined types 2, 9, 10, 11, and 12). Moderate and poor predictors of ischemia were fractures consisting of four fragments (accuracy, 0.67), angular displacement of the head (accuracy, 0.62 for angulations over 45 degrees ), the amount of displacement of the tuberosities (accuracy, 0.61 for displacement over 10 mm), glenohumeral dislocation (accuracy, 0.49), head-split components (accuracy, 0.49), and fractures consisting of three fragments (accuracy, 0.38). When the above criteria (anatomic neck, short calcar, disrupted hinge) were combined, positive predictive values of up to 97% could be obtained. The most relevant predictors of ischemia were the length of the dorsomedial metaphyseal extension, the integrity of the medial hinge, and the basic fracture type determined with the binary description system.

Adult↗
PubMed2005

Reduced osteoblastic population and defective mineralization in osteopetrotic (op/op) mice.

Osteopetrotic (op/op) mice fail to exhibit bone remodeling because of a defective osteoclast formation due to a lack of macrophage colony-stimulating factor. In this study, we investigated the femora of op/op mice to clarify whether the osteoblastic population and bone mineralization are involved in osteoclasts or their bone resorption. The op/op mice extended the meshwork of trabecular bones from the chondro-osseous junction to the diaphyseal region. In the femoral metaphyses of op/op mice, intense alkaline phosphatase (ALPase)-positive osteoblasts were observed on the metaphyseal bone in close proximity to the erosion zone of the growth plates. Von Kossa's staining revealed scattered mineralized nodules and a fine meshwork of mineralized bone matrices while the wild-type littermates developed well-mineralized trabeculae parallel to the longitudinal axis. In contrast to the metaphysis, some op/op diaphyses showed flattened osteoblasts with weak ALPase-positivity, and the other diaphyses displayed bone surfaces without a covering by osteoblasts. It is likely, therefore, that the osteoblastic population and activity were lessened in the op/op diaphyses. Despite the osteopetrotic model, von Kossa's staining demonstrated patchy unmineralized areas in the op/op diaphyses, indicating that a lower population and/or the activity of osteoblasts resulted in defective mineralization in the bone. Transmission electron microscopy disclosed few osteoblasts on the diaphyseal bones, and instead, bone marrow cells and vascular endothelial cells were often attached to the unmineralized bone. Osteocytes were embedded in the unmineralized bone matrix. Thus, osteoclasts appear to be involved in the osteoblastic population and activity as well as subsequent bone mineralization.

Alkaline Phosphatase↗
PubMed2006

Perinatal exposure to PCB 153, but not PCB 126, alters bone tissue composition in female goat offspring.

The aim of this study was to investigate if environmentally relevant doses of the putative estrogenic non dioxin-like PCB 153 and the dioxin-like PCB 126 caused changes in bone tissue in female goat offspring following perinatal exposure. Goat dams were orally dosed with PCB 153 in corn oil (98 microg/kg body wt/day) or PCB 126 (49 ng/kg body wt/day) from day 60 of gestation until delivery. The offspring were exposed to PCB in utero and through mother's milk. The suckling period lasted for 6 weeks. Offspring metacarpal bones were analysed using peripheral quantitative computed tomography (pQCT) after euthanisation at 9 months of age. The diaphyseal bone was analysed at a distance of 18% and 50% of the total bone length, and the metaphyseal bone at a distance of 9%. Also, biomechanical three-point bending of the bones was conducted, with the load being applied to the mid-diaphyseal pQCT measure point (50%). PCB 153 exposure significantly decreased the total cross-sectional area (125 mm(2)+/-4) versus non-exposed (142 mm(2)+/-5), decreased the marrow cavity (38 mm(2)+/-4) versus non-exposed (50 mm(2)+/-3) and decreased the moment of resistance (318 mm(3)+/-10) versus non-exposed (371 mm(3)+/-20) at the diaphyseal 18% measure point. At the metaphyseal measure point, the trabecular bone mineral density (121 mg/cm(3)+/-5) was increased versus non-exposed (111 mg/cm(3)+/-3). PCB 126 exposure did not produce any observable changes in bone tissue. The biomechanical testing of the bones did not show any significant changes in bone strength after PCB 153 or PCB 126 exposure. In conclusion, perinatal exposure to PCB 153, but not PCB 126, resulted in altered bone composition in female goat offspring.

Administration, Oral↗