Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “BONES”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 559 records · Page 31Linked to original sources
PubMed1998

Histological integration of allogeneic cancellous bone tissue treated by supercritical CO2 implanted in sheep bones.

UNLABELLED: Different chemical or physical methods of bone processing have been developed to decrease the antigenicity of allogeneic bone which may delay or prevent graft integration. We have developed a method based on delipidation and deproteination of the bone with a supercritical fluid and hydrogen peroxide. Cylinders of cancellous allogeneic bone treated in this way were implanted for four weeks, four months or eight months in holes drilled in sheep condyles or tibial plateau. Histological sections were then processed and analysed qualitatively and quantitatively using an image analysis software coupled to a light microscope. Measurements were made of the trabecular bone surface (BS/TS), the relative osteoid surface (OS/BS), the active osteoid surface (OS/BS), active resorption surface (Oc.S/BS) and the relative surface of newly formed bone. After four weeks, the control cylinders (non-treated allogeneic bone) had been invaded by cellular tissue composed of lymphocytes and plasmocytes surrounding remnants of the donor bone marrow tissue. The processed cylinders showed osteoid apposition at the surface of their external trabeculae. The trabecular bone and osteoid surfaces were significantly higher in the processed bone sections than in the control bone sections. After four months, most of the control material had been osteolysed and replaced by connective tissue containing lymphocyte islets, while the processed materials showed a large amount of bone synthesized at the surface of implant trabeculae which appeared fragmented and disseminated within the newly formed bone. All the histomorphometric parameters measured were significantly different from those of the control. By eight months, most of the control material had been totally osteolysed with very little bone ingrown in the implantation site. Only one control implant had been integrated. The processed cylinders were difficult to discern from the bone in which they were implanted. The parameters measured on the processed cylinders were significantly higher than those measured on the control sections. IN CONCLUSION: the treatment applied to the bone enhanced allogeneic bone integration and could provide a new kind of tissue treatment for bone banking.

Animals↗
PubMed2003

Biochemical markers of bone metabolism in bone marrow edema syndrome of the hip.

The aim of this study was to evaluate bone metabolism in patients with bone marrow edema syndrome of the hip. In 37 consecutive patients undergoing core decompression of the femoral head, biochemical markers of bone metabolism were measured in aspirates from cancellous bone and in samples obtained simultaneously from peripheral blood. The diagnosis was made by means of radiographs, magnetic resonance imaging (MRI), and core biopsy specimens. Undecalcified microtome section were available for histopathological evaluation. Bone specific alkaline phosphatase (bone ALP), osteocalcin (OC), procollagen Type I N-terminal propeptide (PINP), and C-terminal cross-linking telopeptide (ICTP) were studied. Mean serum levels of analytes were 13.1 ng/mL (OC), 11.2 ng/mL (bone ALP), 4.7 ng/mL (ICTP), and 38.8 ng/mL (PINP). In samples obtained from cancellous bone, mean concentrations of all markers were elevated significantly. The mean bone to serum ratios for bone ALP and OC were 14.1 (P=0.005) and 4.1 (P=0.002), respectively. For collagen Type I metabolites, bone to serum ratios averaged 16.3 (P=0.001) for ICTP and 9.6 (P=0.001) for PINP. Markers of bone formation correlated with each other in serum as well as in aspirates from cancellous bone. Elevation of all markers in aspirates from cancellous bone pointed at increased bone turnover, which correlated with histopathological findings of irregularly woven bone, osteoid seams, and lining cells. Mean serum concentrations of all markers, however, were not different from healthy individuals and thus did not provide any useful clue in the diagnosis of this disease. The lack of osteonecrotic regions in our specimens, the marked increase of bone turnover in samples obtained from edematous lesions, and the fact that none of the patients developed osteonecrosis of the femoral head so far seem to further support the contention that transient bone marrow edema syndrome of the hip is a distinct clinical entity.

Adult↗
PubMed2006

Bone metabolism markers predict increase in bone mass, height and sitting height during puberty depending on the VDR Fok1 genotype.

OBJECTIVES: Longitudinal growth and bone mass accumulation are two important phenomena during puberty, resulting in attainment of peak bone mass (PBM) and final height. They are thought to be under strong genetic control, with the vitamin D receptor (VDR) gene being among the candidate genes. Bone metabolism markers are reported to be good predictors of longitudinal growth and bone mass increase. The purpose of this longitudinal study was to evaluate whether bone metabolism markers predict bone mass and height increase differently according to Fok1 VDR genotype throughout puberty in healthy adolescents. PATIENTS AND MEASUREMENTS: At the start of the study 130 girls were aged 10.8 (range 8.5-12.8) years and 125 boys were aged 11.8 (range 9.4-14.6) years at the first visit. Markers of bone formation and bone resorption were measured at the first visit, as well as height and sitting height (SH), and bone mineral content (BMC) of the lumbar spine, femur, arm and total body. All measurements were repeated after 2 years. RESULTS: A higher BMC of the femur, distal arm and total body was found in ff boys at the first visit, which was not related to higher levels of bone metabolism markers in this group. In girls, no differences between genotypes were seen in BMC (increase). However, concentrations of markers of bone formation [alkaline phosphatase (AP), bone-specific alkaline phosphatase (BAP), procollagen aminoterminal propeptide (PINP)] and bone resorption [type I carboxyterminal telopeptide (ICTP)] were higher in ff girls. Regression coefficients between bone metabolism markers and bone mass increase differed according to genotype and sex. A similar pattern was found for height and SH (increase), the latter as a representative of growth of the axial skeleton, mainly consisting of cancellous bone. CONCLUSIONS: Our data suggest that the predicting capacities of bone metabolism markers on bone mass (increase), height and SH (increase) are genotype dependent. Their use as predictors of final height or PBM therefore remains questionable without knowing the genotype.

Adolescent↗
PubMed2005

Pamidronate prevents bone loss and decreased bone strength in adult female and male rats fed an isocaloric low-protein diet.

UNLABELLED: Isocaloric dietary protein deficiency is associated with decreased BMD and bone strength as well as depressed somatotroph and gonadotroph axis. Inhibition of increased bone resorption by the bisphosphonate pamidronate in rats fed an isocaloric low-protein diet fully prevents bone loss and alteration of bone strength. INTRODUCTION: Isocaloric dietary protein deficiency is associated with decreased BMD and bone strength as well as depressed somatotroph and gonadotroph axis. This negative bone balance is the consequence of increased bone resorption and decreased bone formation. Whether inhibition of bone resorption could prevent low-protein diet-induced bone loss and alteration of biomechanics is not known. MATERIALS AND METHODS: The effect of the bisphosphonate pamidronate was studied in 5.5-month-old female or 6-month-old male rats pair-fed a control (15% casein) or an isocaloric low-protein (2.5% casein) diet for 19 and 26 weeks, respectively. Pamidronate (0.6 mg/kg) was given subcutaneously 5 days/month for 4 months in female rats or for 5 months in male rats. BMD, microarchitecture, and bone strength were measured at the level of the proximal and midshaft tibia. Urinary deoxypyridinoline excretion, serum osteocalcin, and IGF-I were also measured. RESULTS: The increase in bone resorption in female rats (+100%) and in male rats (+33%) fed a low-protein diet was prevented by pamidronate treatment. The reduced osteocalcin levels observed in rats fed a low-protein diet were further decreased in both female (-34%) and male (-30%) rats treated with pamidronate. The bone turnover decrease induced by pamidronate prevented bone strength reduction, trabecular bone loss, microarchitecture, and BMD alterations induced by the isocaloric low-protein diet. Similar effects were observed at the level of the midshaft tibia. Significant decrease of plasma IGF-I was observed in rats fed a low-protein diet independently of the pamidronate treatment. CONCLUSION: In conclusion, inhibition of increased bone resorption in rats fed an isocaloric low-protein diet fully prevents bone loss and alteration of bone strength.

Amino Acids↗
PubMed2001

High-turnover periprosthetic bone remodeling and immature bone formation around loose cemented total hip joints.

Aseptic loosening and periprosthetic osteolysis are the major problems awaiting solution in total hip surgery. The clinical investigation focused on the analysis of periprosthetic bone remodeling to clarify one important key event in the cascade of periprosthetic connective tissue weakening and osteolysis around loose artificial hip joints. Twelve acetabular bone samples adjacent to granulomatous synovial-like membrane of loose hip prosthesis were retrieved at revision surgery and processed for Villanueva bone staining for morphological observation and bone histomorphometric analysis. Eight well-fixed bony samples were used as control. Although osteoclastic surface and eroded surface by osteoclasts were evident in the periprosthetic bone from loose hip joints (p = 0.003 and p = 0.027), increased osteoid/low-mineralized bone matrix (p < 0.001) and osteoid width (p < 0.001) also were significant findings in structural analysis. In addition, not only elevated mineral apposition rate (MAR; p = 0.044) but also increased mineralizing surface (p = 0.044) and bone formation rate (BFR; p = 0.002) in loose periprosthetic bones were shown in dynamic data analysis. These results were confirmed by precise morphological observation by confocal laser scanning microscopy. Active coupling of bone formation and resorption and increased osteocytes with abundant bone canalicular projections were found in combined with the presence of immature bone matrices (osteoid and low-mineralized bone areas) in periprosthetic bones from loose hip joints. These results indicated that active osteoclastic bone resorption and/or defective bone formation are coupled with monocyte/macrophage-mediated foreign body-type granuloma in the synovial-like interface membrane of loose hip joints. Thus, this unique high-turnover periprosthetic bone remodeling with bad bone quality probably is caused by the result of cellular host response combined with inappropriate cyclic mechanical loading. The fragile periprosthetic bone may contribute to hip prosthesis loosening.

Aged↗
PubMed1999

Osseointegration around titanium screws placed into the areas between guided bone augmented sites compared with osseointegration around guided bone graft augmented sites in rabbit tibia.

The aim of this study was to compare the degree of osseointegration around titanium screws placed into the areas between guided bone augmented sites and guided bone graft augmented sites in 8 Japanese white rabbit tibia. The skin and periosteum were incised and lifted to expose the inner surfaces of both tibia. Eight rabbits were divided into 2 groups: 1) a guided bone augmentation (GBA) group of 2 rabbits, and 2) a guided bone graft augmentation (GBCA) group of 6 rabbits. In the GBA group, the bone marrow was penetrated several times in both tibial bones. Three titanium screws were inserted into the bone so that the top of each screw was 3 mm above the bone surface and covered with an expanded polytetrafluoroethylene membrane (ePTFE). In the GBGA group autogenous cortical bone (10 mm x 10 mm x 1 mm) was taken from the left tibia and grafted on the inner surface of the right tibial bone, titanium screws being similarly inserted. The surgical site was covered by ePTFE. After healing for 2 months, the animals were euthanatized, and the experimental area was prepared for histological investigation. New bone had formed on the surgical sites in the GBA group and grafted bone had survived in the GBGA group, with no sign of infection or membrane exposure. The degree of osseointegration around the screw was 67.6 +/- 11.2% (mean +/- SD) in the GBA group and 78.8 +/- 11.9% in the GBGA group. There was no significant difference between the groups (p = 0.29). The ratio of mineralized bone to bone marrow was 45.7 +/- 6.2% in the GBA group and 64.4 +/- 4.4% in the GBGA group. There was a significant difference between the groups (p < 0.05). Although there was no significant difference for osseointegration around the screw placed into the GBA and GBGA sites, the quality of newly generated bone or grafted bone was quite different. Therefore, we suggest that predictable bone augmentation beyond the bone surface can be achieved by either the GBA or the GBGA procedure with ePTFE. However, it was difficult to conclude which procedure was superior with respect to the osseointegration around the titanium screw.

Animals↗
PubMedDate not supplied

Lesions of bone and bone marrow in myeloid leukosis occurring naturally in adult broiler breeders.

Lesions of bone and bone marrow in myeloid leukosis (ML) occurring naturally in adult broiler breeders were investigated pathologically. During gross examination, nodules and protrusions were commonly observed on the surface of the sternum, ribs, vertebrae, and synsacrum. The bone marrow of all the bones of the body was pale in color. Histologically, granulated myelocytes proliferated in the bone marrow of various bones and in the periosteum of the sternum, ribs, vertebrae, and synsacrum. The first proliferation of tumor cells occurred in the bone marrow of epiphysis. The myelocytes invaded through haversian and Volkmann's canals from the bone marrow to periosteal areas. Hematopoiesis was suppressed by marked proliferation of tumor cells in the bone marrow of the whole bone. Atrophy was also seen in the bones, including medullary bones of the chickens suffering from ML. Proliferation of myelocytes was seen in the bone marrow and periosteum of ossified cartilaginous rings of the trachea and larynx. Marked proliferation of myelocytes was seen in the dura mater of spinal cords, and it subsequently depressed the spinal cords. Bone formation with cartilage was seen in the periosteum of the sternum having marked proliferation of myelocytes in the bone marrow and periosteum. Ultrastructurally, tumor cells showed large nuclei and cytoplasm with large round electron-dense lysosomes. The virus particles were rarely detected in the cytoplasm of tumor cells. The polymerase chain reaction test of tumor samples showed positive for subgroup J avian leukosis virus. This study indicates that the myelocytes can invade through the compact bones to the periosteum in the sternum, ribs, vertebrae, synsarcum, and ossified cartilage of trachea and larynx having thinner compact bones. In addition, the periosteal osteogenesis with cartilage in the sternum may be reactive change against the bone atrophy because of the marked proliferation of myelocytes.

Animals↗
PubMed2003

[Treatment of large bone defect of radius with vascularized tubulate periosteum graft and bone filling material in rabbits].

OBJECTIVE: To study the treatment efficacy of vascularized periosteum graft and bone filling material for long bone defect. METHODS: Forty young and forty adult rabbits were divided into four groups respectively according to the bone filling materials. A 3 cm long segment was removed from the middle part of the rabbit radius to make a bone defect model. The periosteum was reserved and restored to set up a vascularized tubulate periosteum graft. On the left side, autogenous bone graft, decalcified allograft, tricalcium phosphate, and hydroxyapatite were used to fill in the bone defect respectively; on the right side, no bone filling material was used as controls. The repairing effect of bone defect was evaluated by roentogenography, biomechanical, and histological methods. RESULTS: In young rabbits, bone defects on both sides healed in the 6th week after operation. The bending strength of radius in the tricalcium phosphate group and in the hydroxyapatite group were lower in the 12th week and there was significant difference when compared with autogenous bone graft group, decalcified allograft group and control group (P < 0.05). The repairing mechanism included intramembranous and endochondral ossification, and intramembranous ossification was prevalent. In the adult rabbits, the repairing rates of bone defect were 50% in the autogenous bone graft group, 40% in the decalcified allograft group, 30% in the tricalcium phosphate group and in the hydroxyapatite group and 42.5% in the control group, respectively. CONCLUSION: In young rabbits, large bone defect can be repaired with vascularized tubulate periosteum graft with or without the combining use of bone filling materials. The bone filling material which will be substituted slowly is disadvantageous to the recovery of bone strength. In adult rabbits, vascularized tubulate periosteum graft combined with bone filling materials can not repair the large bone defect effectively.

Animals↗
PubMed1994

Bone tissue composition: biochemical anatomy of bone.

Bone is chemically built up as a mineralized matrix which comprises collagen and a small amount of noncollagenous proteins. This paper points out some useful methods to evaluate the bone composition. Demineralizing extraction of bone powder with EDTA allows the determination of matrix size and degree of extractability. These parameters vary with bone type, anatomical site of the bone, disease, species, and drug treatment. The study of bone particles in situ can be done by separation of bone powder according to their density. A shift of the bone particles to higher density fractions reflects an increased amount of older, more mineralized osteons in the bone with its consequences on the mechanical competence of the bone. Quantity and quality of bone matrix mineralization are related to bone cell activity which can be studied indirectly by further exploration of the composition of the bone matrix. Many noncollagenous proteins are buried in the extracellular bone matrix from where they can be released when bone is resorbed. These proteins can then act on bone cells in an autocrine or paracrine manner. Altered concentrations of noncollagenous proteins in bone matrix are described in three pathological conditions associated with changes in other bone properties: osteoarthritis, osteopenia, and osteogenesis imperfecta. The functional significance and origin of these changes will have to be subjected to further study.

Animals↗
PubMed1992

Restoring and maintaining bone in osteopenic female rat skeleton: I. Changes in bone mass and structure.

This experiment contains the crucial data for the lose, restore, and maintain (LRM) concept, a practical approach for reversing existing osteoporosis. The LRM concept uses anabolic agents to restore bone mass and architecture (+ phase) and then switches to an agent with the established ability to maintain bone mass, to keep the new bone (+/- phase). The purpose of this study was to learn whether switching to an agent known chiefly for its ability to maintain existing bone mass preserves new bone induced by PGE2 in osteopenic, estrogen-depleted rats. The current study had three phases, the bone loss (-), restore (+), and maintain (+/-) phases. We ovariectomized (OX) or sham ovariectomized (sham-OX) 5.5-month-old female rats (- phase). The OX rats were treated 5 months postovariectomy with 1-6 mg PGE2 per kg/day for 75 days to restore lost cancellous bone mass (+ phase), and then PGE2 treatment was stopped and treatment began with 1 or 5 micrograms/kg of risedronate, a bisphosphonate, twice a week for 60 days (+/- phase). During the loss (-) phase, the cancellous bone volume of the proximal tibial metaphysis in the OX rat fell to 19% of initial and 30% of age-matched control levels. During the restore (+) phase, the cancellous bone volume in OX rats doubled. When PGE2 treatment was stopped, however, and no special maintenance efforts were made during the maintain (+/-) phase, the PGE2-induced cancellous bone disappeared. In contrast, the PGE2-induced cancellous bone persisted when the PGE2 treatment was followed by either a 1 or 5 micrograms treatment of risedronate per kg given twice a week for 60 days during the maintain (+/-) phase. The tibial shaft demonstrated very little cortical bone loss during the loss (-) phase in OX rats. The tibial shaft cortical bone fell some 8%. During the restore (+) phase, new cortical bone in OX rats increased by 22%. When PGE2 treatment was stopped and nothing was given during the maintain (+/-) phase, however, all but the PGE2-induced subperiosteal bone disappeared. In contrast, when PGE2 treatment was stopped and 1 micron risedronate per kg twice a week for 60 days was administered during the maintenance (+/-) phase, the PGE2-induced subperiosteal bone and some of the subendocortical bone and marrow trabeculae persisted.(ABSTRACT TRUNCATED AT 400 WORDS)

Aging↗
PubMed2001

Histomorphometric description of allograft bone remodeling and union in a canine segmental femoral defect model: a comparison of rhBMP-2, cancellous bone graft, and absorbable collagen sponge.

The purpose of this study was to determine the effect of recombinant human bone morphogenetic protein type 2 (rhBMP-2) on the histomorphometry of femoral allograft-host bone union and allograft remodeling. A 6 cm mid-diaphyseal femoral defect was created and filled with an allograft stabilized with an interlocking nail in 21 dogs. Dogs were randomly divided into three equal groups and the allograft-host bone junctions and the mid-diaphyses of the allografts were treated with either an absorbable collagen sponge (ACS) loaded with rhBMP-2 (BMP group), an autogenous cancellous bone graft (CBG group), or ACS loaded with buffer solution (ACS group). All dogs received daily tetracycline until sacrifice at 24 weeks to label new bone formation. Histomorphometric analyses on sections of proximal and distal allograft-host bone junctions and the mid-diaphyseal portion of allografts were performed using fluorescent and regular light microscopy. Analyses of the host bone and junctions between allograft and host bone revealed significantly greater new bone formation and larger osteon radii in the BMP group compared to CBG and ACS groups and contralateral intact bone. Porosity in CBG and ACS groups was significantly higher than in the BMP group, which had similar values to intact bone. In transverse sections of allografts, the largest pore diameters were present in the CBG group. Based on all parameters measured, significantly higher bone turnover occurred in the outer cortical area of the allograft in all groups as compared to the inner cortical and mid-cortical areas. New bone formation and osteon radius/osteon width in allografts were similar for all three groups. Higher porosity and larger pore diameters in the CBG and ACS groups suggested higher bone resorption versus formation in these groups compared to the BMP group. The results of this study reveal more balanced allograft bone resorption and bone formation in the BMP group, with greater resorptive activity in the CBG and ACS groups. However, neither rhBMP-2 nor autogenous bone graft increased allograft incorporation when compared to the negative control (ACS group).

Absorbable Implants↗
PubMed1998

Immunolocalization and quantification of noncollagenous bone matrix proteins in methylmethacrylate-embedded adult human bone in combination with histomorphometry.

The noncollagenous proteins (NCPs) in the bone matrix comprise growth factors with distinct cellular effects and a series of proteins with less clear biological actions. In order to understand the role of these proteins in bone metabolism and in bone diseases, it is crucial to determine their localization and quantity in normal and pathological bone. We have developed an immunohistochemical method to detect osteopontin, osteocalcin, bone sialoprotein, osteonectin, decorin, biglycan, and the growth factors transforming growth factor-beta, insulin-like growth factor-I, and bone morphogenetic protein-2 both in bone matrix and in bone cells of adult human bone embedded in methylmethacrylate. Immunohistochemistry and standard bone histomorphometry in adjacent sections allows the localization of the proteins to metabolically active sites in bone. The protocol works with several fixatives and with bone specimens obtained and embedded to over 20 years ago. Most importantly, we developed a procedure to specifically stain the mineralized matrix green in combination with a red staining of the NCPs. Using digital image analysis it is possible to quantify the relative amounts of NCPs (microm2 NCP area/microm2 mineralized matrix area). Within one biopsy of normal bone cut at four different heights (at a distance of 100 microm), two adjacent sections were stained either for osteopontin or osteonectin. Thirty trabecular and 20 cortical microscopic fields were measured, and the NCP:mineralized matrix ratio was calculated. Stepwise analysis of the standard error of the mean of the NCP:mineralized matrix ratios showed that measuring about 50 microscopic fields is sufficient to obtain representative data with a small confidence interval. In conclusion, the present procedure enables to quantify NCPs and to relate their presence to metabolically active sites in bone. The quantification provides the opportunity to monitor differences in distribution (e.g., cortical vs. trabecular) and differences between normal and pathological conditions and to assess changes in matrix composition during treatment. This can be done by reanalyzing bone biopsies obtained in the past, e.g., during clinical trials. Therefore, the present technique will be a valuable tool for the study of noncollagenous bone matrix proteins in human bone.

Adult↗
PubMed1998

Is all bone the same? Distinctive distributions and properties of non-collagenous matrix proteins in lamellar vs. woven bone imply the existence of different underlying osteogenic mechanisms.

The purpose of this review is to summarize recent functional and structural findings regarding non-collagenous matrix proteins in bone and teeth, to compare gene locations for bone and tooth matrix proteins with loci for hereditary skeletal diseases, and to present several provocative hypotheses which integrate this new information into a physiological context. Hypothesis I proposes that the molecular composition of rapidly deposited and mineralized woven bone, as well as the responsiveness of cells synthesizing woven bone to stimuli, is different from that for more slowly synthesized lamellar bone, implying the existence of distinctive osteogenic mechanisms. This review of recent research strongly supports this proposal. Briefly, the protein composition of woven bone matrix is enriched in acidic phosphoproteins BAG-75 and BSP, which are not expressed in lamellar bone, which is itself enriched in osteocalcin. De novo deposition and mineralization of woven bone occurs faster than in lamellar bone by means of a matrix-vesicle-assisted mechanism. Deposition of woven bone occurs at sites experiencing biomechanical strains higher than those experienced by lamellar bone. In addition, woven bone in metaphyseal regions is more susceptible to osteoclastic resorption after space flight, ovariectomy, and loss of weightbearing than is lamellar bone. Finally, osteoprogenitor cells responsive to parathyroid hormone reside in the metaphyseal region of long bones. Taken together, these findings suggest that Hypothesis I represents a useful paradigm for future studies. Specific functions mediated by most individual bone and tooth matrix proteins remain uncertain. A review of current literature suggests that the functionality of skeletal matrix proteins is expressed through specific binding sites composed of particular species-conserved structural motifs (Hypothesis 2). Examples include the previously recognized Asp-Ser-Ser motif of dentin phosphophoryns and the gamma-carboxyglutamic acid motif of matrix GLA protein and osteocalcin. A new polyacidic amino acid motif composed of consecutive Asp and Glu residues (n > 7) was defined in extracellular matrix components osteopontin, bone sialoprotein, and bone acidic glycoprotein-75 on the basis of strong functional analogies with similar polyacidic stretches in divalent metal storage proteins of the endoplasmic reticulum and sarcoplasmic reticulum. These structural motifs represent prime targets for future structure-function studies in vivo and in vitro.

1-Carboxyglutamic Acid↗
PubMed1989

Flurbiprofen enhances growth and cancellous and cortical bone accumulation in rapidly growing long bones.

The effects of flurbiprofen, a non-steroidal anti-inflammatory drug, on bone growth was studied by static and dynamic histomorphometry in immature (28 days old) male Sprague-Dawley rats. Flurbiprofen at 0, 0.02, 0.1, 0.5 or 2.5 mg/kg/d doses was given subcutaneously daily for 21 days. The 0.1 and 0.5 mg/kg/d doses were most effective in stimulating longitudinal and radial bone growth and enhancing the accumulation of cancellous and cortical bone. Proximal tibial longitudinal bone growth rate, growth plate thickness, and periosteal bone formation rate were increased 30-40%, while cortical bone (tibial shaft) and cancellous bone (proximal tibial metaphysis) accumulated 12% and 90% more bone than controls, respectively. Enhanced accumulation of cortical bone was attributed to stimulated periosteal bone formation without accompanying marrow cavity enlargement. Enhanced accumulation of cancellous hard tissue was postulated to be due to reduced trabecular bone resorption and no effect on bone formation. The cell counts support these conclusions. There was a decrease in osteoclast numbers (-62 to -70%), an insignificant decrease in osteoblast numbers (-5 to -30%) per mm of bone surface and a decrease in osteoclast to osteoblast ratio (-35 to -56%). The findings presented are compatible with the conclusion that flurbiprofen, induced changes in rapidly growing long bones by reducing osteoclast activity and recruitment, stimulating longitudinal and radial growth, increasing the cortical bone mass by stimulated periosteal bone growth and depressed endosteal resorption, and increasing cancellous bone mass by depressed trabecular bone resorption without affecting bone formation.

Animals↗
PubMed2002

The role of estrogen receptor-beta, in the early age-related bone gain and later age-related bone loss in female mice.

The molecular and cellular mechanism of estrogen action in skeletal tissue remains unclear. The purpose of this study was to understand the role of estrogen receptor-beta, (ERbeta) on cortical and cancellous bone during growth and aging by comparing the bone phenotype of 6- and 13-month-old female mice with or without ERbeta. Groups of 11-14 wild-type (WT) controls and ERbeta knockout (BERKO) female mice were necropsied at 6 and 13 months of age. At both ages, BERKO mice did not differ significantly from WT controls in uterine weight and uterine epithelial thickness, indicating that ERbeta does not regulate the growth of uterine tissue. Femoral length increased significantly by 5.5% at 6 months of age in BERKO mice compared with WT controls. At 6 months of age, peripheral quantitative computerized tomography (pQCT) analysis of the distal femoral metaphysis (DFM) and femoral shafts showed that BERKO mice had significantly higher cortical bone content and periosteal circumference as compared with WT controls at both sites. In contrast to the findings in cortical bone, at 6 months of age, there was no difference between BERKO and WT mice in trabecular density, trabecular bone volume (TBV), or formation and resorption indices at the DFM. In 13-month-old WT mice, TBV (-41%), trabecular density (-27%) and cortical thickness decreased significantly. while marrow cavity and endocortical circumference increased significantly compared with 6-month-old WT mice. These age-related decreases in cancellous and endocortical bone did not occur in BERKO mice. At 13 months of age, BERKO mice had significantly higher total, trabecular and cortical bone, while having significantly lower bone resorption, bone formation and bone turnover in DFM compared with WT mice. These results indicate that deleting ERbeta protected against age-related bone loss in both the cancellous and endocortical compartments by decreasing bone resorption and bone turnover in aged female mice. These data demonstrate that in female mice, ERbeta plays a role in inhibiting periosteal bone formation, longitudinal and radial bone growth during the growth period, while it plays a role in stimulating bone resorption, bone turnover and bone loss on cancellous and endocortical bone surfaces during the aging process.

Journal Article↗
PubMed1996

Biochemical markers of bone turnover reflect femoral bone loss in elderly women.

Although over 90% of hip fractures occur in patients over age 70, few data are available on femoral bone loss in this age group. To examine the relationship between biochemical markers of bone turnover and femoral bone loss in the elderly, 36 female and 17 male, healthy, community-dwelling elderly over age 65 (mean +/- SD age: women 71 +/- 4 years, men 75 +/- 5 years) were followed for 3 years. Annual bone mineral density measurements of the hip and lumbar spine by dual-energy x-ray absorptiometry (DXA) were obtained and biochemical markers of bone resorption (urinary N-telopeptide crosslinks, free pyridinoline, total pyridinoline, total deoxypyridinoline, and hydroxyproline) and bone formation (serum osteocalcin, bone-specific alkaline phosphatase) were obtained at the end of year 3. In elderly women, longitudinal bone loss at the total hip was negatively correlated with markers of bone resorption (r = -0.39 to -0.52, P < 0.05), bone formation (r = -0.38, P < 0.05), and age (r = -0.39, P < 0.05). Markers of bone resorption were correlated with markers of bone formation (r = 0.63 to 0.74, P < 0. 01). In multiple regression analysis, urinary N-telopeptide crosslinks (marker of resorption), serum osteocalcin (marker of formation), and serum parathyroid hormone explained 43% of the variability of bone loss at the total hip in women. These parameters were not related to bone loss in men. We conclude that femoral bone loss increases with age in women over 65. Measurements of specific biochemical markers of bone turnover are correlated with longitudinal bone loss in elderly women. These markers may help identify women at greatest risk for bone loss who would benefit most from therapeutic interventions.

Aged↗
PubMed1990

Prostaglandin E2 enhances cortical bone mass and activates intracortical bone remodeling in intact and ovariectomized female rats.

To assess the efficacy of prostaglandin E2 (PGE2) in augmenting cortical bone mass, graded doses of PGE2 were subcutaneously administered for 30 days to seven-month old sham-ovariectomized (SHAM) and ovariectomized (OVX) rats. Both groups were operated at three months of age. Histomorphometric analyses of double fluorescent labeled tibial shafts were performed on basal control, OVX, and SHAM rats treated with 0, 0.3, 1, 3, and 6 mg PGE2/kg/d for 30 days. Baseline aging data showed increased cortical tissue and cortical bone area and reduced bone formation parameters at the periosteal and endocortical bone envelopes between three and eight months of age. The tibial shafts of OVX rats compared to SHAM controls showed elevated periosteal mineral apposition rate and endocortical bone formation parameters. PGE2 administration to OVX and SHAM rats increased cortical bone by the addition of new circumferential bone on the endocortical and periosteal surfaces, as well as woven cancellous bone in the marrow region. Stimulated osteoblastic recruitment and activity enhanced bone formation at all bone surfaces. The new bone was both lamellar and woven in nature. PGE2 treatment also activated intracortical bone remodeling (not seen in untreated eight-month old rats), creating a porous cortex. Thus, PGE2 administration activated cortical bone modeling in the formation mode (A----F), as well as intracortical bone remodeling (A----R----F). PGE2 administration to OVX rats resulted in more intracortical bone remodeling, periosteal bone formation, and new cancellous bone production than observed in PGE2 treated controls. The findings that PGE2 administration to OVX and intact female rats increases cortical bone mass, coupled with observations that mouse, rat, dog, and man respond similarly to PGE2, suggest that PGE2 administration may be useful in the prevention and treatment of postmenopausal osteoporosis.

Aging↗
PubMed2002

Regulating DeltaFosB expression in adult Tet-Off-DeltaFosB transgenic mice alters bone formation and bone mass.

The DeltaFosB isoforms are naturally occurring AP-1 family members that increase bone volume via a cell-autonomous effect on osteoblastic bone formation. Mice overexpressing DeltaFosB demonstrate a very high level of bone formation, resulting in a progressive osteosclerosis. Despite the linkage of bone formation and resorption in physiological systems, no alteration in bone resorption was detected in mice overexpressing DeltaFosB. To determine whether altering DeltaFosB expression can regulate bone formation independently of bone resorption in adult mice, we used the Tet-Off-inducible transgene system to induce or block transgenic DeltaFosB overexpression and thereby regulate bone formation in vivo. Overexpression of DeltaFosB after skeletal maturity increased trabecular bone volume by increasing bone formation, again without altering bone resorption, indicating that developmental DeltaFosB overexpression is not required for the osteosclerotic phenotype. Similarly, switching off DeltaFosB overexpression after osteosclerosis had developed led to a marked decrease in bone formation and loss of bone mass such that trabecular bone volume approached normal levels. Despite this dramatic reduction, no alteration in bone resorption was detected. These results clearly demonstrate that DeltaFosB regulates bone formation and bone mass in adult mice with no effect on bone resorption.

Animals↗