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PubMed1996

Transforming growth factor beta and bone morphogenetic protein 2 for bone ingrowth: a comparison using bone chambers in rats.

We compared the ability of transforming growth factor beta 1 (TGF beta 1) and bone morphogenetic protein 2 (BMP-2) to increase the penetration distances for fibrous tissue and bone into porous coralline hydroxyapatite. Forty-four rats received pairs of titanium bone chambers implanted bilaterally in their proximal tibiae. These chambers allow tissue ingrowth from one end of a long cylinder, so that ingrowth distances along the cylinder axis can be measured. Since bone never grows as far as fibrous or undifferentiated mesenchymal tissue, we measured both total tissue ingrowth and bone ingrowth distances. All chambers were implanted with cylinders of porous hydroxyapatite (Interpore 200). The hydroxyapatite cylinders were treated with either 1, 33, or 1000 ng of TGF beta 1 or BMP-2 prior to implantation, and compared with untreated contralateral control implants at 6 weeks. The bone ingrowth distance into the porous hydroxyapatite showed a trend toward inhibition with TGF beta 1 as compared to untreated controls (p < 0.08), and there was a negative correlation between TGF beta 1 dose and ingrowth distances for both bone (p < 0.01) and total tissue (p < 0.01). BMP-2 greatly increased bone (p < 0.001) and total tissue (p < 0.001) ingrowth distances.

Animals↗
PubMed2001

Bone, bone marrow, and MIBI scintigraphic findings in Gaucher's disease "bone crisis".

PURPOSE: The authors report the utility of Tc-99m MIBI imaging in Gaucher's disease, which results in the accumulation of glucocerebroside in macrophages. Inflated macrophages, or Gaucher's cells, involve the reticuloendothelial organs. MATERIALS AND METHODS: A 38-year-old man with type I Gaucher's disease, splenectomy, and early bone involvement was examined for a low back "bone crisis." He had a history of total left hip replacement. Results of pelvic radiographs were normal. Magnetic resonance imaging showed complete infiltration of the bone marrow in the lumbar spine and the sacrum. The left iliac bone, the sacrum, and the adjacent part of L5 showed heterogeneously decreased uptake on bone scintigraphs. Hematopoietic bone marrow was absent in these regions and in the left femur. No infection of the prosthesis was revealed with labeled granulocytes. RESULTS: Avascular necrosis in the left iliac bone was diagnosed, which is a very unusual location. There was no uptake of MIBI in the iliac bones or the femurs. CONCLUSION: These findings suggest that MIBI may not be a good tool for the evaluation of medullary infiltration by Gaucher's cells.

Adult↗
PubMed1979

Bone formation by revascularized periosteal and bone grafts, compared with traditional bone grafts.

Three groups of dogs were studied to compare the bone formation obtained with traditional bone grafting techniques, and that obtained with revascularized periosteum or revascularized bone grafts--all in unstressed bone. Revascularized periosteum did not produce a significant amount of bone in this unstressed model. At 4 months the revascularized rib grafts had a slightly greater tolerance to stress at the callus site than traditional bone grafts, but the incidence of non-union was the same. We conclude that the use of revascularized bone grafts should be reserved for situations in which traditional bone grafting techniques are unlikely to be successful.

Animals↗
PubMed2005

Role of bovine bone morphogenetic proteins in bone matrix protein and osteoblast-related gene expression during rat bone marrow stromal cell differentiation.

Bone morphogenetic proteins (BMPs) are known to promote osteogenesis, and clinical trials are currently underway evaluating the ability of certain BMPs to promote bone graft and fracture healing. To observe the mechanism of osteoinductive and bone formation, 100 microg of bovine BMP was tested during osteogenic differentiation of rat bone marrow stromal cells (MSCs) and C2C12 line culture for 14 and 28 days. We examined alkaline phosphatase (ALP) by assay, immunohistochemical studies for bone matrix proteins, and mRNA expression of bone matrix proteins and osteoblast-related analysis by reverse-transcription polymerase chain reaction. ALP activity in MSC cultures was elevated by bovine BMP by two to fivefold (P < 0.05-0.001). DNA and protein content increased over 14 days. BMP significantly increased the mRNA expression of type I collagen, ALP, osterix, osteocalcin, osteopontin, vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF)-A, and parathyroid hormone receptor time dependently during the osteoblastic differentiation. There was no markedly enhanced mRNA expression of bone sialoprotein (BSP) and glyceraldehyde-3-phosphate dehydrogenase compared with that of control. Immunohistochemical results also showed BMP increased immunoreactive positivity of type I collagen, osteocalcin, osteonectin, osteopontin, and BSP during the C2C12 differentiation. These data indicated that BMP enhances our ability to stimulate the differentiation of osteoblast-like cells and increases osteoinductivity, bone matrix protein formation and mineralization, angiogenesis, and chondrogenesis during osteoblast progenitor cell differentiation in vitro and that the role of chondrogenic is weak.

Alkaline Phosphatase↗
PubMedDate not supplied

Placement of endosseous implants into bone-grafted alveolar clefts: assessment of bone bridge after autogenous particulate cancellous bone and marrow graft.

The objective of this study was to evaluate the bone quantity of alveoli grafted with autogenous particulate cancellous bone and marrow for implant placement in patients with alveolar clefts. Bone height, bone width, and interdental alveolar crest level were evaluated using computed tomography and periapical radiographs. The grafted alveoli underwent resorption 3-dimensionally, and the interdental alveolar crest level also decreased. The latter seemed to be the critical factor for implant surgery, as almost half of the grafted alveoli required another bone graft within 24 months after the original bone graft to increase the interdental alveolar crest level for endosseous implant placement. These data suggest that alveoli grafted with particulate cancellous bone and marrow are suitable for implant placement, but that the loss of width and height of the bone bridge must also be considered.

Adolescent↗
PubMed2003

Clodronate stimulates bone formation as well as inhibits bone resorption and increases bone mineral density in rats fed a low-calcium diet.

The pharmacological actions of bisphosphonates are due to the inhibitory effects on bone resorption, but little is known about the bisphosphonate action on bone formation. The purpose of this study is to elucidate the actions of bisphosphonates, clodronate, on bone formation in the experimental in vivo and in vitro rat models. The bone mineral density (BMD) was decreased in the rats fed a low-calcium diet (0.05% Ca) for 6 days compared with the rats fed a normal-calcium diet (0.5% Ca). The decrease in BMD was suppressed in the 2 mgP/day and the 4 mgP/day clodronate administrations. Bone formation rate (BFR) in rats fed a low-calcium diet was significantly increased compared with the rats fed a normal-calcium diet, and the 2 mgP clodronate administration further increased the BFR. In the cultured rat bone marrow cells, the area of mineralized nodules was significantly increased at 10(-7) and 10(-6) M clodronate, but high concentration of clodronate decreased the area. From these results, it is concluded that clodronate stimulates bone formation when the drug was given to a rat with a relatively lower dose that is sufficient to prevent bone resorption and that this effect may be due to the stimulatory effect on the differentiation process of osteoblasts.

Alkaline Phosphatase↗
PubMed1992

[Distribution of bone morphogenetic protein in human bone and tooth germs: analysis of specificity of monoclonal antibody against bone morphogenetic protein].

A cell strain stably secreting monoclonal antibody against BMP was obtained by hybridoma technique. The monoclonal antibody specifically reacted with the cells of human bone and tooth germs on paraffin embedded tissue sections. Immunohistochemical staining shows that BMP is distributed along collagen fibres in normal bone, also exist in osteoid tissue of new bone, in osteoblasts and in the cells of bone marrow. BMP may be found in human tooth germs such as in predentin, in the cells of outer and inner enamel epithelium, in the cells of dental sac generating alveolar bone. The results demonstrate that generation and growth of human bone and development of tooth germs have relation to BMP. The results at the molecular level prove that some antigenic determinants of human and bovine BMP are the same. BMP function activity inhibition test suggests that this antibody may block the function group of BMP. The ability of the monoclonal antibody to detect antigen and to inhibit generation of new bone makes it potentially useful in purification of BMP and in treating osteosarcoma and other bone tumors.

Animals↗
PubMed1979

The bone inductive capacity of various bone transplanting materials used for treatment of experimental bone defects.

The bone defect repairing capacities of autogenous cancellous bone (ACB), decalcified bone (DB), autodigested "low-antigenic" bone matrix (LBM) and preserved bone (PB) were tested in experimental defects in rabbit scapulae. The healing of the defects was most effective with ACB transplants as judged by roentgenologic and microscopic studies. The DB and LBM transplants caused states of healing comparable to each other, and the PB transplants showed the least satisfactory results in this experiment. The ACB, DB and LBM transplants caused bone induction, which resulted in the formation of new bone, subsequent resorption of the transplanted material and rapid reshaping of the callus. The PB transplants caused no bone induction; only some growth of callus on the edges of the defect was observed and pieces of the transplanted material were seen as late as 10 weeks after the operation as dead particles encapsulated by fibrous tissue. The infiltrations of inflammatory cells around the PB transplants indicated a considerable host versus graft reaction whereas this reaction was less with the other materials tested.

Animals↗
PubMed2001

No bone ingrowth into the tibia tunnel in anterior cruciate ligament-reconstructed patients: a 1-year prospective quantified CT study of 10 patients reconstructed with an autologous bone-patellar tendon-bone graft.

10 patients with major instability symptoms due to an acute anterior cruciate ligament injury were operated on with a bone-patellar tendon-bone reconstruction. Tibial condyle bone mineral density (BMD), bone ingrowth and changes in diameter in the tibia bone tunnel were studied with quantified computed tomography (QCT) postoperatively and after 1, 3, 6 and 12 months. We found no sign of bone ingrowth in the form of increased bone mineral density (BMD) in the bone tunnels in any of the patients. The tunnel diameter increased in all patients during the first postoperative months. After 1 year, 5 patients had a smaller diameter than at the first postoperative examination, 2 had the same diameter as immediately after surgery and 2 patients had a larger diameter. A sclerotic zone developed in all patients along the perimeter of the tunnel during the 3-6 months of follow-up. The BMD in the tibial condyle decreased at 3 months; it then increased, but between 6 and 12 months, it levelled out and was slightly lower than postoperatively. In conclusion, we found no growth of bone into the tunnel and tendinous part of the graft during the first postoperative year.

Adult↗
PubMed2000

Autologous bone marrow stromal cells loaded onto porous hydroxyapatite ceramic accelerate bone repair in critical-size defects of sheep long bones.

The ability of marrow-derived osteoprogenitor cells to promote repair of critical-size tibial gaps upon autologous transplantation on a hydroxyapatite ceramic (HAC) carrier was tested in a sheep model. Conditions for in vitro expansion of sheep bone marrow stromal cells (BMSC) were established and the osteogenic potential of the expanded cells was validated. Ectopic implantation of sheep BMSC in immunocompromised mice led to extensive bone formation. When used to repair tibial gaps in sheep, cell-loaded implants (n = 2) conducted a far more extensive bone formation than did cell-free HAC cylinders (n = 2) over a 2-month period. In cell-loaded implants, bone formation was found to occur both within the internal macropore space and around the HAC cylinder while in control cell-free implants, bone formation was limited mostly to the outer surface and was not observed in most of the inner pores. As tested in an indentation assay, the stiffness of the complex HAC-bone material was found to be higher in cell-loaded implants compared to controls. Our pilot study on a limited number of large-sized animals suggests that the use of autologous BMSC in conjunction with HAC-based carriers results in faster bone repair compared to HAC alone. Potentially this combination could be used clinically in the treatment of extensive long bone defects.

Animals↗
PubMed1998

The effects of bone plug length and screw diameter on the holding strength of bone-tendon-bone grafts.

The effect of bone plug length and Kurosaka screw (DePuy, Warsaw, IN) diameter on graft holding strength of the bone-tendon-bone construct was determined. Random length porcine bone plugs were assigned to fixation with 7 or 9 mm Kurosaka screws. Peak load to failure was determined. There was a significant decrease in peak load to failure of the 5-mm long bone plugs compared with longer bone plugs. No difference was found between longer lengths of bone plug in either the 7- or 9-mm screw diameter groups. The 9-mm diameter screws significantly increased peak load to failure for both 1- and 2-cm bone plug lengths.

Animals↗
PubMed2003

Bone density changes in Paget's disease 2 years after iv pamidronate: profound, sustained increases in pagetic bone with severity-related loss in forearm nonpagetic cortical bone.

Bone mineral density (BMD) was measured at three sites (forearm, spine, and hip) using dual X-ray and single-photon absorptiometry in 68 patients with Paget's disease before and after treatment with iv pamidronate. Patients were treated according to the severity of their disease; the mild category (Group I, hydroxyproline excretion (Hyp(E)) <5.0 micromol/L GF) received 120 mg, the moderate category (Group II, Hyp(E) 5.0-9.99 micromol/GF) 180 mg, and the severe category (Group III, > or = 10.0 micromol/GF) 240 mg. Group I was followed for 1 year, and both Groups II and III for 2 years. At the lumbar spine in pagetic bone there were no differences between groups in early responses, with a profound increase 6 months after treatment 20.5 +/- 2.0% above baseline values to 1.403 +/- 0.063 g/cm(2) (mean +/- SEM)(P < 0.001). This increase in BMD was sustained to 2 years (1.355 +/- 0.078 g/cm(2), P < 0.001) and was 15.0 +/- 2.2% above baseline values. The pagetic total hip BMD increased after treatment in all groups, with a mean rise of 10.4 +/- 1.4% at 1 year to 1.505 +/- 0.083 g/cm(2) (P < 0.01). At the pagetic femoral neck the response was similar, with a peak significant rise at 1 year of 10.7 +/- 1.7% to 1.403 +/- 0.097 g/cm(2) (P < 0.01). In nonpagetic spinal bone there were no differences between the group responses, with a combined mean increase of 4.3 +/- 0.7% at 1 year to 0.999 +/- 0.027 g/cm(2) (P < 0.01). In both Groups II and III the increase in BMD was significantly higher than baseline values at 1 and 2 years (P < 0.01). In the nonpagetic total hip BMD remained unchanged over the 2-year period and likewise, there were no significant changes from baseline at the nonpagetic femoral neck site. In the nonpagetic forearm we found a significant loss in BMD at the ultradistal (mainly trabecular), midregion (80% cortical), and proximal shaft (95% cortical) sites in Group III, persisting to 2 years at the latter two sites. The increase in bone density in pagetic bone, persisting at least 2 years, provides a new modality of assessment of the response of pagetic bone to treatment and suggests a mechanism for the reduction in fracture risk in such bone after effective bisphosphonate treatment. Severity-dependent nonpagetic forearm bone loss, persisting to 2 years at cortical sites, suggests a potential drug-induced fracture risk at the forearm and possibly elsewhere in the absence of appropriate preventive cotreatment.

Aged↗
PubMed1990

Estrogen inhibition of periosteal bone formation in rat long bones: down-regulation of gene expression for bone matrix proteins.

Estrogen is important for both the sexual dimorphism of the skeleton during growth and the maintenance of bone balance in adults. This report describes the in vivo effects of estrogen on bone formation and gene expression in the tibial diaphysis of ovariectomized rats. Rats were ovariectomized at 8 weeks of age and were given diethylstilbestrol (DES) or placebo 1 week later as sc sustained release pellets. Histomorphometry revealed that that the periosteal bone formation and apposition rates were reduced at the tibial diaphysis 1 week after beginning estrogen treatment and further reduced after 2 weeks. Interestingly, DES treatment had no effect on endosteal bone formation, but suppressed endosteal bone resorption. Northern analysis of freshly isolated periosteal cells from tibiae and femora revealed that DES treatment resulted in dramatic decreases in steady state mRNA levels for the bone matrix proteins osteocalcin, prepro alpha 2(I) chain of type 1 collagen, osteonectin, and osteopontin as well as the osteoblast marker enzyme alkaline phosphatase. The results suggest that the inhibitory effects of estrogen on radial bone growth in rats are mediated, or at least accompanied, by the inhibition of the expression of bone matrix protein genes in periosteal cells.

Alkaline Phosphatase↗
PubMed2003

Genistein prevents bone resorption diseases by inhibiting bone resorption and stimulating bone formation.

UNLABELLED: Genistein, a soybean-derived isoflavone, has been shown to suppress osteoclastic bone resorption. To clarify the mechanisms underlying this action, we investigated the effects of genistein on the differentiation, cytoskeleton and function in mice osteoclasts in vitro and bone metabolism in ovariectomized rats. STUDY DESIGN: Primary OCs were isolated from 3 week-old mice and induced by 1,25(OH)(2)D(3). Then OCs were exposed to genistein at various concentration of 0 M, 10(-9) M, 10(-8) M, 10(-7) M, 10(-6) M, and 10(-5) M. The number of TRAP+ cells were counted as well as the surface area of bone resorption on bone slice. F-actin change was observed by Confocal. In vivo, forty 12 week-old female SD rats were randomly assigned to four groups: (1) sham operated (Sham); (2) (OVX); (3) ovariectomized and treated with estradiol (OVX-E); (4) ovariectomized and received genistein (OVX-G). After 12 weeks, BMD, body weight, serum level of alkaline phosphatase (ALP), acid phosphatase (ACP), osteocalcin (OC), IL-1beta, TNFalpha, IL-6 and calcitonin (CT) were evaluated. Femur were sectioned. In addition, the serum estradiol, the weight of uteri and histological behavior were also examined to indicate the side effect of genistein to the uteri. RESULTS: In vitro, the number of TRAP+ cells decreased depending on the concentration of genistein as well as the area of bone resorption. F-actin became disorder under Confocal. In vivo, after treated with genistein, BMD and the serum level of ALP, ACP, osteocalcin increased significantly, while the serum level of IL-1beta and TNFalpha decreased. Especially, the increase of ALP and osteocalcin of OVX-G was higher than that of OVX-E. Histologically, the pachy-trabecula were observed as well as the more mineral deposition lines. Additionally, the uterus weight index and the serum estradiol in OVX-G rats were lower significantly than those of OVX-E. The epithelia of uteri gland in OVX-G appeared cubic while those of OVX-E became squamous. CONCLUSIONS: Genistein can prevent bone resorption diseases by the promotion of bone formation and the prevention of bone resorption with slight side effect.

Absorptiometry, Photon↗
PubMed2002

BMP 2--Genetics Institute/ Medtronic-Sofamor Danek/Integra. Bone morphogenetic protein 2--Genetics Institute/ Medtronic-Sofamor Danek/Integra, INFUSE Bone Graft, recombinant human bone morphogenetic protein 2--Genetics Institute/Medtronic-Sofamor Danek/Integra, RhBMP 2--Genetics Institute/Medtronic-Sofamor Danek/Integra.

Genetics Institute (Wyeth) is collaborating with Medtronic-Sofamor Danek (which specialises in spinal reconstruction) and Integra Life Sciences to develop a BMP 2 product [INFUSE Bone Graft] for use in spinal reconstruction in North America. The INFUSE Bone Graft product has been approved for use in lumbar interbody spinal fusion procedures in the USA and is in phase III trials for use in lumbar posterolateral spinal fusion procedures. During the procedure, damaged disc is replaced with a collagen sponge (Integra's Absorbable Collagen Sponge) soaked with BMP 2, which is held in place within an implanted cage device (LT-CAGE Lumbar Tapered Fusion Devise); the fusion process subsequently requires several months to complete. However, the patient is able to leave hospital the day after the operation, whereas in conventional spinal surgery a longer recovery time is required. The procedure supersedes the use of autograft bone as it uses a recombinant human bone morphogenic protein, rhBMP-2, which induces the body to grow its own bone where required. Genetics Institute has cloned and expressed bone morphogenic proteins 1-7 and established manufacturing processes by recombinant DNA technology. Bone morphogenic proteins may be useful in the treatment of osteoporosis and orthopaedic trauma. BMP 2 is also being developed for bone regeneration as an implanted device and as an injectable formulation. Genetics Institute is also collaborating with Integra LifeSciences to develop a formulation of BMP 2 with Integra's absorbable collagen-based structures for fracture treatment, which is awaiting approval in the USA.

Bone Morphogenetic Protein 2↗
PubMed2003

Restoration of large bone defects using a hard-setting, injectable putty containing demineralized bone particles compared to cancellous autograft bone.

An injectable, hard-setting, calcium sulfate-based putty containing demineralized bone matrix particles (AlloMatrix II, Wright Medical Technology, Inc, Arlington, Tenn) was compared to autogenous cancellous bone graft to evaluate healing in a canine model. Area fraction of new bone, modulus of elasticity, and compressive strength of new bone were evaluated, as was radiographic and histologic healing. Bilateral defects were created in the proximal humeri, and each defect was implanted with either the putty or autogenous bone according to a randomized schedule. Dogs were euthanized at 6, 13, and 26 weeks. The area fraction, modulus of elasticity, and compressive strength of newly formed bone was not significantly different between the putty and autogenous bone at 6, 13, or 26 weeks. The putty had excellent handling characteristics, was biocompatible, and was as effective as autograft bone in achieving near complete bony restoration of a large, critical-sized defect.

Animals↗
PubMed1998

[Processing of ceramiclike xenogeneic bone and experimental study of its bone formation from composite graft combined with bone marrow].

Ceramiclike xenogeneic bone (CXB) was obtained from the fresh bone of pig ribs being treated by physical and chemical methods to deprive of its organic substance. The CXB possessed the same natural porous network system as that of the human. The CXB was cultured with the bone marrow stromal cells of rabit. When the marrow cells had integrated with the CXB, thus a new material was obtained. (CXB-BM), and was implanted sacro-spinal muscle of rabbit. The specimens were observed under phase microscope, light microscope and electronic scanning microscope. The results showed that: at the 2nd week after the implantation of CBX-BM composite material there began the new bone formation, and the rate of bone formation was increased with time. There was evident new bone formation after 24 weeks. The process of the new bone formation were quite similar to the composite graft of HAP red autogenous and marrow, but the former degraded faster and formed typical cancellous structure earlier. There was no new bone formation when CXB was implanted alone in the control. Both the mechanism of osteogenetic potential and its clinical application were discussed.

Animals↗
PubMed1979

[Reaction of articular cartilage to subchondral defect filling with autologous cancelous bone, Kiel's bone chips and bone cement].

Equally sized subchondral osseous defects were produced in 30 adult rabbits. The defects were filled with autologous cancellous bone, bone cement, or macerated heterologous cancellous bone. Twelve weeks later those filled with autologous cancellous bone showed consolidation with preservation of the subchondral border line. There were no degenerative changes of the joint's cartilage. Filling with bone cement or heterologous cancellous bone, on the other hand, led to destruction of the joint's cartilage. The defects treated with heterologous cancellous bone had not reached osseous consolidation at that time. These results suggest that effective treatment of subchondral osseous defects can only be achieved by filling with autologous cancellous bone.

Animals↗