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At least 1,441 records · Page 80Linked to original sources
PubMed1989

Autogeneic cancellous bone grafts in extensive segmental ulnar defects in dogs. Effects of xenogeneic bovine bone morphogenetic protein without and with interposition of soft tissues and interruption of blood supply.

Xenogeneic (bovine) bone morphogenetic protein (bBMP) and associated insoluble noncollagenous proteins (NCP) were implanted in inbred adult beagle dogs with 3-4 cm diaphyseal defects in the ulna. Defects were stabilized with internal plate fixation, and the control defects were not stabilized. The defects were implanted with either autogeneic cancellous bone grafts (ACG), bBMP/NCP, or a composite of ACG and bBMP/NCP. Of the plated ulnae, 18 of 19 ACG controls restored bone continuity; six of seven defects healed under the influence of bBMP/NCP plus ACG. Two of four defects with bBMP/NCP plus ACG healed and two were filled with osseous tissue, but fibrous tissue developed at one or both bone ends. Eight of nine defects implanted with bBMP/NCP capsules alone were repaired with fibrous tissue only. Of the nonplated defects, four were implanted with bBMP/NCP plus ACG and only one regenerated; three of four showed hypertrophic bone growth around a pseudarthrosis. Of six nonplated defects implanted with bBMP/NCP without ACG, all developed atrophic bone ends and fibrous tissue repair. Thus, to restore continuity of large segmental defects three times greater than the critical size for spontaneous regeneration, xenogeneic bBMP/NCP failed to induce bone regeneration in dogs. To exclude cell-mediated immune reactions and soft-tissue ingrowth, one defect was bridged with a polytetrafluoroethylene semipermeable tube (pore size 0.45 micron) containing implants of bBMP/NCP. In response to bBMP/NCP, cells from the host bone ends produced ossicles of induced woven bone formation. The observation that bBMP/NCP induced bone formation across the defect inside of semipermeable cylindrical chambers suggests that the experiments on bone defects larger than the critical size for spontaneous repair should be repeated with: (1) allogeneic dog BMP/NCP; (2) semipermeable cylinders to protect against muscle interposition; (3) compartment angiograms to evaluate blood supply; (4) treatment of the recipient with immunosuppressants and immunostaining to observe the concentration gradient of BMP; and (5) histologic observations on the first three days after implantation to evaluate cell-mediated immune barriers to the response of BMP.

Animals↗
PubMed1988

Deconvoluted X-ray diffraction analysis of bone and mixtures of bone and particulate hydroxyapatite.

Recent evidence suggests that bone phosphate exists almost entirely as hydroxyapatite (HA). The relative deficiency of calcium and presence of substantial HPO2-4 in bone phosphate indicates modification of the ideal HA structure, however. An inability to resolve closely spaced lines in fine grained materials, coupled with the limited periodicity of the thin mineral crystals of bone have prevented definitive characterization of the structure of bone mineral using standard X-ray diffraction (XRD) techniques. We have applied computer deconvolution XRD techniques to aid in the resolution of component overlapped profiles from bone, synthetic hydroxyapatite (HA) and mixtures of bone and synthetic HA resulting from implantation studies. In the course of this resolution process separate profiles were resolved from the (002) profile of bone derived HA. The ratio of integrated intensities of these profiles to the intensity of the profile of synthetic HA appears to provide an approximate measure of the ratio of bone to synthetic HA in a given sample. The finding of shoulders on the (002) peak of bone provides the basis for resolution into separate profiles. The asymmetry of these shoulders in mature bone cannot be attributed to crystallinity, particle size, or computer artifact. The same finding has been previously reported in hydrolyzed, deproteinated bone. Further work will be needed to resolve the question of whether the structural heterogeneity implied by profile geometry is the result of multiple HA phases, surface layer structure involving hydrolysis and calcium absences, or some other factor.

Animals↗
PubMed1995

Bone morphogenetic proteins, bone marrow stromal cells, and mesenchymal stem cells. Maureen Owen revisited.

In postnatal mammals, there are persistent molecular signals and responding cells in bone to initiate osteogenesis and repair in response to trauma. The responding osteogenic precursor cells are of 2 categories: determined and inducible. The latter can be induced by demineralized bone matrix to form bone. Demineralized bone matrix consists of extracellular matrix and tightly associated bone morphogenetic proteins. The genes for bone morphogenetic proteins have been cloned, the recombinant proteins have been expressed, and currently their mechanism of action is being explored. Bone morphogenetic proteins are pleiotropic initiators of inducible osteogenic precursor cells. Bone morphogenetic proteins govern the 3 key steps in the osteogenic cascade: chemotaxis, mitosis, and differentiation. The receptors for bone morphogenetic proteins have been cloned and expressed and consist of 2 classes, Types I and II, that are membrane bound serine/threonine protein kinases. Bone morphogenetic proteins bind to extracellular matrix and their collaborative action on osteogenic cells culminates in the terminal differentiation of the osteoblast-osteocyte continuum. Bone morphogenetic proteins are currently on the threshold for clinical applications.

Animals↗
PubMed1996

Bone sialoprotein peptides are potent inhibitors of breast cancer cell adhesion to bone.

Bone and bone marrow are important sites of metastasis formation in breast cancer. Extracellular matrix proteins with attachment properties are generally believed to play a key role in tumorigenesis and metastasis formation. We have investigated whether mammary carcinoma cells (MDA-MB-231) can recognize constructs of the fairly bone-specific human bone sialoprotein, which encompass the RGD sequence (EPRGD-NYR). Exogenously added bone sialoprotein peptides with this amino acid sequence in their backbone structure, but not the more common fibronectin-derived GRGDS peptide, strongly inhibited breast cancer cell adhesion to extracellular bone matrix at micromolar concentrations. Most cyclic derivatives with the EPRGDNYR sequence were more effective inhibitors of tumor cell adhesion to bone than their linear equivalents. Furthermore, changes in the RGD-tripeptide of the backbone structure of the constructs, removal of the NYR flanking sequence, or a different tertiary cyclic structure significantly decreased their inhibitory potencies. In addition, the RGE-analogue EPRGENYR was capable of inhibiting breast cancer cell adhesion to bone, albeit to a lesser extent. We conclude therefore, that the inhibitory potency of the bone sialoprotein-derived peptides on breast cancer cell adhesion to bone is not solely due to a properly positioned RGD-motif alone but is also determined by its flanking regions, together with the tertiary structure of the EPRGDNYR peptide. Synthetic cyclic constructs with the EPRGDNYR sequence may, therefore, be potentially useful as antiadhesive agents for cancer cells to bone in vivo.

Amino Acid Sequence↗
PubMed1996

[Transplantation of pedicled pisiform bone to replace lunate bone with aseptic necrosis].

OBJECTIVE: To find out a new and effective method for the treatment of aseptic necrosis of lunate bone. METHODS: Blood supply and morphology of pisiform bone were investigated in 25 upper limbs and 57 sets of carpal bone from adult cadavers on the basis of anatomical study. The lunate bone was replaced with pisiform bone of pedicled blood vessel and tendon of musculus flexor earpiulnaris in 17 patients with aseptic necrosis of lunate bone (stage III). RESULTS: The patients were followed up for 18-46 months (average of 28 months). Complete relief of pain was obtained in all of the patients, and the range of motion of their wrists was improved. Grip strength was increased by 48.2%. Radiograph showed normal location of transferred pisiform bone without osteosclerosis and atrophy in 16 patients. Atrophy of pisiform bone was found 2 years after operation in one patient. In the 17 patients, 15 resumed their original jobs and 2 changed their jobs for other reasons. CONCLUSION: We consider that the carpal bone chain can be completely preserved by transplantation of pedicled pisiform bone, which it is an effective method to treat aseptic necrosis stage III of lunate bone.

Adult↗
PubMed2001

High-dose chemotherapy shows a dose-dependent toxicity to bone marrow osteoprogenitors: a mechanism for post-bone marrow transplantation osteopenia.

BACKGROUND: Osteoporosis is a sequela of hemopoietic cell transplantation with a complex multifactorial pathogenesis in which the relative role of chemotherapy and irradiation is not completely understood. Therefore, the authors investigated the toxicity of chemotherapy-only conditioning regimens on bone homeostasis and bone marrow osteoprogenitors, its dose dependency, and the mechanism of chemotherapy-induced osteopenia. METHODS: Fifty-one patients with high-grade non-Hodgkin lymphoma or breast carcinoma who had been treated previously with high-dose + peripheral blood progenitor cell or conventional chemotherapy or who had not received any treatment (prechemotherapy) were enrolled. The authors measured the bone marrow colony-forming unit fibroblast (CFU-f) and long-term culture-initiating cell frequency, forearm bone mineral density, serum osteotropic hormones and metabolic markers of bone formation (plasma osteocalcin), and resorption (urinary collagen I C-crosslinks). RESULTS: Both high-dose chemotherapy regimens caused a 50% reduction in CFU-f frequency, independently of gonadal function status, whereas conventional chemotherapy and prechemotherapy groups were unaffected. Bone mineral density was measured in 26 non-Hodgkin lymphoma patients and again only high-dose chemotherapy caused a 10% loss in cortical bone and 20% in trabecular bone. No endocrine abnormality was found except for the secondary amenorrhea uniformly induced in the high-dose chemotherapy group. In these patients, plasma osteocalcin unexpectedly failed to increase in response to the menopausal increase in bone resorption rate, showing a selective impairment of the osteoblast compartment to cope with increased functional demand. CONCLUSIONS: Chemotherapy without irradiation shows a dose-dependent toxicity to bone marrow stromal osteoprogenitors and can cause osteopenia by direct damage of the osteoblastic compartment, as a mechanism distinct from and summable to hypogonadism.

Adult↗
PubMed2004

Mediation of bone ingrowth in porous hydroxyapatite bone graft substitutes.

Previous investigations have shown that both the early biological response and the mechanical properties of a porous hydroxyapatite bone graft substitute are highly sensitive to its pore structure. The objective of this study was to evaluate whether the pore structure continued to influence bone integration in the medium to long term. Two screened batches of porous hydroxyapatite (PHA) designated as batch A and batch B, with porosities of approximately 60 and 80%, respectively, were selected for this study and implanted for periods of 5, 13, and 26 weeks into the lower femur of New Zealand White rabbits. Histomorphometric analysis of the absolute volume of bone ingrowth within batch A and B implants from 5 to 26 weeks showed that the absolute volume of bone ingrowth was consistently lower in batch A (10-21%), compared to batch B implants (24-31%). However, when the volume of bone ingrowth was normalised for the available pore space, this difference was reduced (23-47% and 32-42% for batches A and B, respectively). These observations suggest that differences in the volume of bone ingrowth initially depended on pore interconnectivity rather than pore size, whereas the volume or morphology of the PHA influenced the volume and morphology of bone ingrowth at later time points. Compression testing showed that bone ingrowth had a strong reinforcing effect on PHA bone graft substitutes, and a strong correlation was identified between mechanical properties and the absolute volume of ingrowth for both batches A and B. Furthermore, at 13 and 26 weeks, there was no significant variation in the ultimate compressive strength of integrated batch A and B implants. This similarity in ultimate mechanical properties indicated that the absolute volume of ingrowth may be mediated by the PHA structure through its impact on the dynamics of the local biomechanical environment. The results of push-out testing showed that fixation of PHA bone graft substitutes was independent of density within the range studied, with no significant difference in the interfacial shear stress between batches A and B at each time point throughout the study.

Animals↗
PubMed1989

Bone demineralization, biochemical indices of bone remodeling, and estrogen replacement therapy in adults with Turner's syndrome.

The study centered on a controversy about whether long-term estrogen replacement therapy may ameliorate the osteoporosis seen in patients with Turner's syndrome. This study comprised 26 adult patients with Turner's syndrome (9 treated and 17 untreated or insufficiently treated) and 12 adult women with pure gonadal dysgenesis (8 untreated and 4 treated). A low bone density below -2 standard deviations from the age- and sex-matched predicted normal mean was documented by dual-photon absorptiometry of the lumbar spine in all the untreated and insufficiently treated patients, but only in 6 treated patients. The biochemical indices of bone resorption (urinary hydroxyproline excretion and plasma tartrate-resistant acid phosphatase activity), as well as osteoblastic function (serum osteocalcin and bone alkaline phosphatase isoenzyme), were significantly increased in untreated and insufficiently treated patients compared with treated patients. A significant negative correlation was found between biochemically documented osteoresorption and spinal bone mineral density corrected for age of the patients. Significant positive correlations were found between serum osteocalcin and bone alkaline phosphatase isoenzyme and between biochemical indices of bone resorption and formation. Although in the patients there was an evidence of a high bone remodeling rate, the rate of bone mass loss seemed to be low, comparable with that seen in oophorectomized women who had already passed their accelerated phase of bone loss. The results indicate that long-term hormonal replacement therapy is justified in gonadal dysgenesis, regardless of the karyotype of the patient, to prevent further bone mass loss.

Acid Phosphatase↗
PubMed1999

Accelerating bone formation and earlier healing after using demineralized bone matrix for limb lengthening in rabbits.

We studied the effects of grafting with demineralized bone matrix during lengthening of the tibia in young Japanese White rabbits. The demineralized bone matrix was made from frozen cortical bone harvested from other rabbits. A 5-mm gap was created in the tibial diaphysis by a subperiosteal osteotomy; a maximum of 20 mm (2-3 mm/day) of tibial lengthening was reached in a week with use of an external fixator. The control group of 20 rabbits did not receive an implant; the group of 21 experimental rabbits received an implant of demineralized bone matrix in the surgical gap. The control group failed to demonstrate radiographic callus 5 weeks after surgery, and nonunion was persistent after 1 year. In the group with demineralized bone matrix, new radiodensity was demonstrated within the lengthening gap at 3 weeks, with a gradual increase in bone density to 85% that of the intact tibia after 12 weeks. Bone union was seen within 1 year for all experimental animals for whom the external fixator was removed 8 weeks after the procedure. These bones showed normal bone structure histologically. The lengthening was carried out at a rapid distraction rate of 2-3 mm/day; therefore, this method allows for satisfactory bone formation at a faster rate than normal.

Absorptiometry, Photon↗
PubMed1979

Effect of preimplantation treatment on the bone-forming potential of decalcified allogeneic and xenogeneic bone-matrix implants.

Bone-forming property of 0.6 M HCl decalcified (a) allogeneic bone matrix preserved in 70% alcohol, (b) allogeneic bone matrix preserved in anaesthetic ether, (c) allogeneic 'Ossein' provided by the Leather Research Institute, Madras, and (d) xenogeneic bone-matrix preserved in alcohol was studied by fitting the implants in surgically created complete circumferential osteo-periosteal gaps in the ulna of rabbits. Bone formation was assessed radiologically, macroscopically, histologically, and by tetracycline fluorescence up to 16 postimplantation weeks. Successful bridging of the gap by new bone formation was observed in 75% of (a) and 28.6% of (d) preserved up to 2 weeks. Ether-preserved implants did not induce bone formation. The 'Ossein' implants remained as inert material neither invaded by host cells nor inducing any bone formation. The xenogeneic implants exhibited local immune response which was probably responsible for poor osteogeneic response. Bone forming quality of bone-matrix implants appears to be influenced by the chemical treatment during preparation and preservation, host cellular response and immune reaction invoked by the implant.

Animals↗
PubMed2001

Response of biochemical markers of bone turnover to estrogen treatment in post-menopausal women: evidence against an early anabolic effect on bone formation.

Bone loss following menopause can be prevented or reduced by estrogen replacement therapy (ERT). The primary action of estrogen on bone is generally considered to be antiresorptive, but some evidence would also suggest a stimulatory effect on bone formation. The aim of this study was to assess the effect of ERT on biochemical markers of bone resorption (urinary pyridinoline and deoxypyridinoline), and of bone formation (bone-specific alkaline phosphatase--B-ALP, and the C-terminal propeptide of type I collagen--CICP) in a group of 25 postmenopausal women with no evidence of osteoporosis. Since the suggested anabolic effect of estrogen seems to take place in the early period of ERT, we measured the response of markers immediately before and after the start of treatment (30, 60, 120 and 180 days). The markers of bone resorption started to decrease at 30 days and remained low thereafter. We also observed a similar decrease in serum levels of B-ALP and CICP, reflecting a reduction of bone formation rate. Our data would indicate that ERT at the given dose does not have early anabolic effects on bone, in addition to its recognized suppressive effect on bone resorption.

Alkaline Phosphatase↗
PubMed2006

Milk basic protein increases bone mineral density and improves bone metabolism in healthy young women.

UNLABELLED: Effect of milk basic protein on bone metabolism in healthy young women. INTRODUCTION: Milk has more beneficial effects on bone health than other food sources. Recent in vitro and in vivo studies have shown that milk whey protein, especially its basic protein fraction (milk basic protein, MBP), contains several components capable of promoting bone formation and inhibiting bone resorption. The object of this study was to examine the effect of MBP on the bone mineral density and bone metabolism of healthy young women. METHODS: Thirty-five healthy young women were randomly assigned to treatment with either placebo or MBP (40 mg per day) for 6 months. The bone mineral density (BMD) of the lumbar vertebrae L2-L4 of each subject was measured by dual-energy X-ray absorptiometry (DXA) at 0 and 6 months of treatment. Serum and urine indexes of bone metabolism were measured at 0, 3 and 6 months. All subjects completed the study in accordance with the protocol. RESULTS: The mean rate of gain of lumbar BMD in the MBP group (1.57%) was significantly higher than in the placebo group (0.13%, P=0.042). When compared with the placebo group, urinary cross-linked N-telopeptides of type-I collagen (NTx) were significantly decreased, and serum osteocalcin was significantly increased in the MBP group at 6 months. CONCLUSION: These results suggested that MBP supplementation was effective in increasing BMD in young women and that this increase in BMD may be primarily mediated through the promotion of bone formation and inhibition of bone resorption by MBP supplementation.

Absorptiometry, Photon↗
PubMed2000

Exercise and mechanical loading increase periosteal bone formation and whole bone strength in C57BL/6J mice but not in C3H/Hej mice.

To identify the genes, and the mechanisms that account for the 53% higher peak bone density in C3H/HeJ (C3H) mice compared with C57BL/6J (B6) mice, we are performing quantitative trait locus and phenotypic analyses. The phenotypic studies revealed differences in bone formation and resorption, and showed that hindlimb immobilization (by sciatic neurectomy) caused a greater increase in endosteal resorption in the tibiae of B6 compared with C3H mice. The current studies were intended to examine the hypothesis that the bones of C3H mice are less sensitive to mechanical loading than the bones of B6 mice. To increase mechanical loading, 9-week-old female B6 and C3H mice (n = 10-13 mice/group) were subjected to a jumping exercise (20 jumps/day, 5 days/week, to heights of 20-30 cm) for a total of 4 weeks. Control mice did not jump. Osteocalcin, alkaline phosphatase (ALP) activity, and IGF-I were measured in serum. The left tibiae were used for histomorphometry (ground cross-sections prepared at the tibiofibular junction) and the right tibiae and femora were used for determinations of bone breaking strength (3-point bending). The results of these studies revealed (1) significant effects of both mouse strain (B6 and C3H) and the jumping exercise on tibial strength; (2) an exercise-dependent increase in serum IGF-I in C3H, but not B6 mice; and (3) no effects on serum ALP or osteocalcin. The histomorphometric analyses showed no effect of exercise on C3H tibiae, but significant exercise-dependent increases in total bone area, periosteal perimeter, periosteal mineral apposition rate (MAR), and periosteal bone formation (P < 0.02 for each) in B6 tibiae. There were no effects of exercise on periosteal resorption or any endosteal measurement in either C3H or B6 mice. Since the jumping exercise was designed to cause a two-three fold increase in muscular-skeletal loading at the tibio-fibular junction, and the calculated stress (g/mm2) at this sampling site was only 16% greater for B6 compared with C3H mice, we had anticipated that both strains of mice would show exercise-dependent increases in periosteal bone formation, with a greater response in the B6 mice. The lack of a response in the C3H tibiae demonstrates that the bones of C3H mice are less sensitive to mechanical loading (and unloading) than the bones of B6 mice.

Alkaline Phosphatase↗
PubMed1998

Plasma leptin values in relation to bone mass and density and to dynamic biochemical markers of bone resorption and formation in postmenopausal women.

After the menopause it has been noted that heavier women conserve bone better than those with lower body weight. The protective effect of obesity on bone mass has been ascribed to a high body fat content. The present study of 54 postmenopausal women was undertaken to determine whether circulating plasma levels of leptin, the newly described hormone produced in adipocytes, were correlated with age-adjusted total body bone mineral content (BMC) or bone mineral density (BMD), or with dynamic biochemical markers of bone resorption or of bone formation. Leptin values were strongly correlated with all measures of adiposity (P < 0.001). Age-adjusted values for BMC and BMD, respectively, were also positively correlated (P < 0.001) with body weight (r = 0.643, r = 0.502), total fat mass (r = 0.557, r = 0.510) and with plasma leptin concentrations (r = 0.480, r = 0.551), confirming a positive relationship between fat mass and bone mass. By contrast, no significant correlations were observed between plasma leptin and dynamic markers of bone resorption (urinary deoxypyridinoline/creatinine r = -0.105, hydroxyproline/creatinine r = -0.193) or formation (plasma osteocalcin r = 0.103). Because there was no evidence for an association between ciculating plasma levels of leptin and biochemical markers of either osteoclastic or osteoblastic activity we conclude it is unlikely that circulating leptin plays any significant direct role in controlling bone cell activity. Our results do not support the hypothesis that leptin mediates the bone-sparing effects of obesity.

Aged↗
PubMed1999

Revascularization and new bone formation in heat-treated bone grafts.

Human imnmunodeficiency virus (HIV) infection is one of the possible serious complications associated with bone allografts. In order to prevent infection, grafted bone is sterilized by various treatments. Heat treatment has attracted attention as a simple and practical method. We carried out a histological study of the influence of heat treatment on autogenic bone grafts. To eliminate the problem of antigenicity of grafted bone, we used autografts, not allografts. Three types of heat-treated autografts were employed: heat-treated at 60 degrees C for 30 min, at 80 degrees C for 10 min, and at 100 degrees C for 5 min; as a control, fresh autografts were replaced in the rabbits' ilium. One, 2, 4 and 8 weeks after grafting, we performed microangiography and prepared two types of samples: transparent and haematoxylin-eosin (H&E) stained. Then, using an image analyzer, we quantitatively measured revascularization and new bone formation in the grafted bone. The grafts heat-treated at 60 degrees C showed early and good revascularization and new bone formation, from 1 to 8 weeks. The grafts heat-treated at 80 degrees C showed relatively good revascularization and new bone formation. However, the grafts heat-treated at 100 degrees C showed unsatisfactory revascularization and bone formation, less than 40% of control 8 weeks after grafting. Therefore, heat treatment at 60-80 degrees C does not seriously affect revascularization and new bone formation.

Animals↗
PubMed2002

Selective synthesis of bone morphogenetic proteins-1, -3, -4 and bone sialoprotein may be important for osteoinduction by Saos-2 cells.

An ability to induce new bone formation at a required site would represent a considerable advance in bone repair and tissue engineering. It has been shown that the healing of critical-size bone defects in rats can be augmented by extracts of Saos-2 cells. These human osteosarcoma cells uniquely contain a bone-inducing activity, whereas other human osteosarcoma cells, e.g., U-2 OS cells, cannot replicate the osteoinductive capacity. To understand the necessary components of the Saos-2 bone-inducing activity, this study compared osteoinductive Saos-2 cells with non-osteoinductive U-2 OS cells with respect to the synthesis of bone morphogenetic proteins (BMPs)-1, -2, -3, -4, -5, -6, and -7 and the non-collagenous matrix proteins bone sialoprotein (BSP), osteonectin (ON), osteopontin (OPN), and osteocalcin (OC). The main differences were abundant synthesis of BMP-1/tolloid, BMP-3, -4, and BSP by Saos-2 cells, but absence or reduced synthesis in U-2 OS cells. BMP-2 and -7 were present in low amounts in both cell types, while BMP-5 and -6 were more abundant in U-2 OS cells, suggesting that these BMPs were of lesser importance for the osteoinductivity of Saos-2 cells. However, a relatively high expression of BMP-3 and -4, together with BMP-1/tolloid, may be important for the osteoinductive capacity of Saos-2 cells. The inability of U2-OS cells to induce bone, despite expressing most of the BMPs, may be due to an insufficiency of tolloid, BMP-3 or -4, BSP, and/or other unknown factors. A better understanding of the necessary components of the Saos-2 cell bone-inducing agent may, in future, lead to clinically useful Saos-2 cell products for bone repair and tissue engineering.

Animals↗
PubMed2006

The application of a murine bone bioreactor as a model of tumor: bone interaction.

A limited number of in vivo models that rapidly assess bone development or allow for the study of tumor progression in a closed in vivo environment exist. To address this, we have used bone tissue engineering techniques to generate a murine in vivo bone bioreactor. The bioreactor was created by implanting an osteoconductive hydroxyapatite scaffold pre-loaded with saline as a control or with bone morphogenetic protein-2 (BMP-2) to the murine femoral artery. Control and BMP-2 bioreactors were harvested and histologically assessed for vascularization and bone formation at 6 and 12 weeks post implantation. BMP-2 significantly enhanced the formation of osteoid within the bioreactor in comparison to the controls. To test the in vivo bone bioreactor as a model of tumor: bone interaction, FVB mice were implanted with control or BMP-2 treated bioreactors. After 6 weeks, an osteolytic inducing mammary tumor cell line tagged with luciferase (PyMT-Luc) derived from the polyoma virus middle T (PyMT) model of mammary tumorigenesis was delivered to the bioreactor via the femoral artery. Analysis of luciferase expression over time demonstrated that the presence of osteoid in the BMP-2 treated bioreactors significantly enhanced the growth rate of the PyMT-Luc cells in comparison to the control group. These data present a unique in vivo model of ectopic bone formation that can be manipulated to address molecular questions that pertain to bone development and tumor progression in a bone environment.

Animals↗
PubMed1985

Metabolic bone disease with and without osteomalacia after intestinal bypass surgery: a bone histomorphometric study.

We performed iliac bone histomorphometry after in vivo double tetracycline labeling 3-14 years after intestinal bypass surgery for obesity in 21 patients, selected because of clinical suspicion of metabolic bone disease, and compared the results with those of 40 age-matched normal control subjects. Osteomalacia defined by rigorous kinetic criteria was found in six cases, histologic features of secondary hyperparathyroidism without significantly impaired mineralization in one case, and possible osteomalacia masked by impaired matrix synthesis in one case. In the patients with definite osteomalacia, nonfracture bone pain was more frequent, corrected plasma calcium lower, plasma alkaline phosphatase and magnesium higher, and secondary hyperparathyroidism more severe than in the other patients. In the patients without osteomalacia there was a 24.5% reduction in trabecular bone volume compared to the controls; in contrast to age-related bone loss and post-menopausal osteoporosis, this was due mainly to reduction in the thickness rather than the density of trabecular plates. About two-thirds of the reduction in trabecular thickness was due to reduction in interstitial bone thickness, representing the cumulative effect of increased depth of osteoclastic resorption cavities, probably due in part to secondary hyperparathyroidism. About one-third of the reduction in trabecular thickness was the result of reduced mean wall thickness, representing insufficient osteoblastic matrix synthesis, probably due in part to malabsorption of an unidentified nutrient necessary for normal bone health. Resorption indices were not increased at the time of the biopsy, but there were persistent defects in the recruitment and activity of osteoblasts. Clinically significant bone loss after intestinal shunt surgery, as in several other clinical situations, results from the combined effects of an unsustained increase in bone resorption and a sustained decrease in bone formation.

Adult↗