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PubMed2003

Remodelling and healing process of moderately heat-treated bone grafts after wide resection of bone and soft-tissue tumors.

INTRODUCTION: In the reconstruction of extensive bone defects after massive resection of malignant musculoskeletal tumors, the clinical results of moderately heat-treated autogenous bone graft have rarely been documented. We evaluated the remodelling and healing process of moderately heat-treated autogenous bone graft by means of imaging features. MATERIALS AND METHODS: The subjects of this study were 19 patients with bone and soft-tissue tumors treated by heat-treated bone graft at our institution between 1992 and 2001, the mean follow-up period was 4.8+/-2.8 years (range 1-9 years). The remodelling and healing process of heat-treated bone graft was evaluated by means of radiography, bone scintigraphy, and MRI. RESULTS: The mean period to obtain bone union between host bone and grafted bone was 9.4 months. Infection was noted in 1 patient, and fracture was present in 2 patients. In 6 patients, pseudoarthrosis was found. Bone scintigraphy showed an increased uptake at the host-graft junction in the period between 3 and 36 months (median 10.7 months) postoperatively. A gradually increased diffuse uptake on the grafted side was evident at an average of 29.1 months (range 19-41 months) postoperatively. High signal intensity on T2-weighted images was observed in the early period after surgery, and iso-intense or low signal intensity became evident after an average of 28.3 months. A gradually increased diffuse uptake on scintigraphy and iso-intense or low signal intensity on T2-weighted images indicated remodelling of the grafted bone. CONCLUSION: Bone union of a moderately heat-treated autogenous bone graft was noted at about 9 months, and its remodelling was proceeding at about 30 months. This method will be useful for bone defects after massive resection of soft-tissue and bone tumors.

Adolescent↗
PubMedDate not supplied

A comparison of microanatomic basis for coupling between bone formation and bone resorption in man and the rat.

The trabecular bone of the secondary spongiosa of mature rats shows a coupling of bone formation to resorption. In adult man the coupling of formation and resorption involves a site-specific sequence of events, in which bone resorption is normally followed, at the same site, by bone formation. Whether the coupled processes of bone resorption and formation also occur at the same site in the rat is unknown. To elucidate the spatial relationship between bone formation and resorption in the rat, we compared the percentage of crenated and non-crenated cement lines with the percentage of crenated and non-crenated bone surfaces in the proximal tibia of adult rats aged 16 weeks-two years. A similar comparison was also made using bone from adult human iliac crest. We found that the trabecular bones of 16-week and seven-month-old rats exhibited a low percentage of crenated cement lines. In contrast, the surfaces of rat bone trabeculae showed a similar low proportion of crenated surface to human bone. However, in older (two years) rats, in which bones have ceased to grow in length, the percentage of cement lines that were crenated increased to towards human levels. These results imply that most of the bone formed in the secondary spongiosa of growing rats occurs on non-resorbed surfaces. Thus, although there is substantial evidence that bone formation is coupled to resorption in the rat, such that increased resorption is associated with increased formation, and suppression of resorption suppresses bone formation, bone formation does not necessarily occur on a previously resorbed site.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1995

Early effects of prostaglandin E2 on bone formation and resorption in different bone sites of rats.

The aim of this study was to determine early effects of prostaglandin E2 (PGE2) on bone mass, formation and resorption in a growing cancellous bone site (the proximal tibial metaphysis, PTM), non-growing cancellous bone site (the distal tibial metaphysis, DTM), and cortical bone site (the tibial shaft, TX) with histomorphometric analysis. Six mg PGE2/kg/d was given s.c. to 6-month-old Sprague-Dawley female rats for 5, 10 or 16 days. Double fluorescent labels were given to 0, 10- and 16-day PGE2 treatment and 16-day control groups. Significant increase in bone mass was found after 16 days treatment in cancellous bone sites but not in the cortical bone site. Stimulated bone formation, indicated by the increase in osteoid perimeter, was observed as early as 5 days post-treatment in all 3 bone sites. Bone formation indices were increased after 10 days of treatment, however, there was no difference in selected bone formation indices between 10 and 16 days PGE2 treatments at all 3 bone sites. Significant increase in eroded surface and eroded surface covered with osteoid was observed in cancellous bone sites after 5 days, but decreased after 10 days of treatment. Although the eroded surface was not elevated in TX at the 5th day, the eroded surface covered with osteoid was increased on endocortical surface which indicated that PGE2 stimulated bone resorption on this surface prior to day 5. We concluded that PGE2 stimulated the bone formation and resorption as early as 5 days post-treatment. The levels of stimulated bone formation was TX > DTM > PTM.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed2006

Morphine and 6-acetylmorphine concentrations in blood, brain, spinal cord, bone marrow and bone after lethal acute or chronic diacetylmorphine administration to mice.

The aim of this study was to evaluate postmortem incorporation of opiates in bone and bone marrow after diacetylmorphine (heroin) administration to mice. Mice were given acute (lethal dose of 300 mg/kg) or chronic (10 and 20 mg/kg/24 h for 20 days) intraperitoneal administration of diacetylmorphine. The two metabolites of diacetylmorphine, 6-acetylmorphine (6-AM) and morphine, were extracted from whole blood, brain, spinal cord, bone marrow and bone (after hydrolysis) using a liquid/liquid method. Quantification was performed by gas chromatography-mass spectrometry (GC/MS). Results showed that after acute administration, opiates were present in all studied tissues. Morphine concentrations appeared to be higher than those of 6-AM in blood (52.4 microg/mL versus 27.7 microg/mL, n=12), bone marrow (87.8 ng/mg versus 8.9 ng/mg, n=6) and bone (0.85 ng/mg versus 0.43 ng/mg, n=6), but 6-AM concentrations were higher than those of morphine in brain (14.0 ng/mg versus 7.4 ng/mg, n=12) and spinal cord (27.8 ng/mg versus 20.8 ng/mg, n=12). No correlation was found for both compounds between blood concentrations and either brain, spinal cord, bone or bone marrow concentrations while a significant one was found between brain and spinal cord concentrations either for morphine (r=0.89, n=12, p<0.001) or 6-AM (r=0.93, n=12, p<0.001), the concentration being higher in spinal cord than in brain. When bones were stored for 2 months, only 6-AM remained in bone marrow but not in bone. After chronic administration, mice being sacrificed by cervical dislocation 24 h after the last injection, no opiate was detected in any studied tissues. Further studies are required, in particular in human bones, but these results seem to show that 6-AM could be detect in bone marrow several weeks after the death and could be an alternative tissue for forensic toxicologist to detect a fatal diacetylmorphine overdose, even if no correlation between blood and bone marrow was observed. On the other hand, neither bone tissue nor bone marrow will allow the confirmation of a chronic diacetylmorphine use.

Analgesics, Opioid↗
PubMed1999

A prospective study of bone loss and turnover after allogeneic bone marrow transplantation: effect of calcium supplementation with or without calcitonin.

Transplantation of solid organs including heart, kidney, and liver is associated with rapid bone loss and increased rate of fracture; data on bone marrow transplantation recipients (BMT) are scarce. The purpose of the present study was to examine the magnitude, timing, and mechanism of bone loss following allogeneic BMT, and to study whether bone loss can be prevented by calcium with or without calcitonin. Sixty-nine patients undergoing allogeneic BMT for malignant blood diseases were enrolled into the study. Forty-four (22 women, 22 men) completed 6 months, and 36 patients 1 year follow-up. They were randomized to receive either no additional treatment (n = 22), or oral calcium 1 g twice daily for 12 months (n = 12) or the same dose of calcium plus intranasal calcitonin 400 IU/day for the first month and then 200 IU/day for 11 months (n = 10). Bone mineral density (BMD) at the lumbar spine and three femoral sites (femoral neck, trochanter, Ward's triangle) was measured by dual-energy X-ray absorptiometry (DXA). Bone turnover rate was followed with markers of bone formation and resorption (serum bone-specific alkaline phosphatase (B-ALP), type I procollagen carboxyterminal (PICP) and aminoterminal propeptide (PINP), serum type I collagen carboxyterminal telopeptide (ICTP)). Serum testosterone was assayed in men. Calcium with or without calcitonin had no effect on bone loss or bone markers; consequently the three study groups were combined. During the first 6 post-transplant months BMD decreased by 5.7% in the lumbar spine and by 6.9% to 8.7% in the three femoral sites (P < 0.0001 for all); no significant further decline occured between 6 and 12 months. Four out of 25 assessable patients experienced vertebral compression fractures. Markers of bone formation reduced: B-ALP by 20% at 3 weeks (P = 0.027), PICP by 40% (P < 0.0001) and PINP by 63% at 6 weeks (P < 0.0001), with a return to baseline by 6 months. The marker of bone resorption, serum ICTP was above normal throughout the whole observation period, with a peak at 6 weeks (77% above baseline, P < 0.0001). In male patients serum testosterone decreased reaching a nadir (57% below baseline) at 6 weeks (P = 0.0003). In conclusion, significant bone loss occurs after BMT. It results from imbalance between reduced bone formation and increased bone resorption; hypogonadism may be a contributing factor in men. Bone loss can not be prevented by calcium with or without calcitonin.

Administration, Inhalation↗
PubMed2001

Bone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase expression in localized human prostatic adenocarcinoma as predictors of clinical outcome: a clinicopathological and immunohistochemical study of 43 cases.

PURPOSE: Skeletal metastases are the hallmark of advanced prostate cancer and recurrence after local surgery is common. Currently to our knowledge no biological markers predict the risk of disease progression in individuals with localized prostate cancer. In a search for predictive markers we evaluated the expression of bone sialoprotein and bone morphogenetic protein 6, 2 bone related proteins, and the angiogenic factor thymidine phosphorylase. MATERIALS AND METHODS: The study population included 43 men who presented with localized prostate cancer treated with radical prostatectomy. Bone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase expression was assessed by immunohistochemical testing. Results were analyzed in relation to pathological disease stage, Gleason score and clinical outcome. Clinical followup was 4.3 to 11.4 years after surgery (median 7.9). RESULTS: Disease did not progress in 17 of the 43 cases, while recurrence and/or metastasis developed in the other 26 at a median of 6.5 and 6.9 years, respectively. Bone sialoprotein and bone morphogenetic protein 6 expression detected in 28 (65%) and 29 (67%) of the 43 samples, respectively, was significantly associated (p = 0.0001). Thymidine phosphorylase detected in 26 samples (60%) was not related to bone sialoprotein and/or bone morphogenetic protein 6 positivity. Bone sialoprotein and/or bone morphogenetic protein 6 expression correlated with bone metastasis, while thymidine phosphorylase expression was related to local recurrence (p = 0.002 and/or 0.007, and 0.00007, respectively). On multivariate analysis only the correlation of thymidine phosphorylase expression with recurrence remained statistically significant (p = 0.002). Co-expression of the 3 markers was observed in the samples of 10 of the 11 patients (90%) with bone metastases and only in 5 of the 17 (29%) who were disease-free. CONCLUSIONS: This study indicates that the expression of bone sialoprotein, bone morphogenetic protein 6 and thymidine phosphorylase determined at a clinically early stage of disease by a simple immunohistochemical technique would enable subgroups of patients to be identified that are at different risks of bone metastasis or recurrence. Detection of such markers would provide additional prognostic information that would be useful for patients with intermediate or low Gleason score or stage disease. These patients would benefit from a more adapted clinical follow-up.

Adenocarcinoma↗
PubMed2005

Bone morphology and vascularization of untreated and guided bone augmentation-treated rabbit calvaria: evaluation of an augmentation model.

OBJECTIVES: Cranial vault is widely used in experimental models on membranous bone healing in general, guided bone augmentation (GBA) studies being one example. To our knowledge, however, few studies on the characteristics of the untreated calvaria regarding bone density, vessel topography, and their intra/interindividual variations and associations are available. The aims of this investigation were to (1) map the large vessel topography of the skull vault, (2) describe the parietal bones of the adult rabbit histologically and morphometrically, and (3) histologically compare untreated parietal bone with parietal bone that had been treated with a GBA device. MATERIAL AND METHODS: Ten adult untreated rabbits were microangiographed. General anesthesia was induced and the mediastinum was opened. Heparin and lidocaine were injected in the aorta followed by perfusion with India ink. After death, en bloc biopsies of the skull vault including the overlying soft tissues and dura mater were taken. The specimens were cleared with the Spalteholtz technique, microscopically examined, and digitally imaged. Thereafter, circular biopsies were harvested to obtain decalcified sections. In addition, sections from 14 GBA-treated rabbit skulls (of the same race, sex and age as the untreated animals) served as reference specimens for comparison. Histomorphometric examinations were carried out. RESULTS: In the cleared specimens, all parietal bones were found to be supplied by one major branch of the meningeal artery. From each of these, separate branches supplied the dura wherein a fine vessel network covered the bone. No major vessels were found in the supracalvarial soft tissue. Numerous fine vessels were found within the periosteum and dura entering the cortical plates. The decalcified sections of the parietal bones revealed an outer and inner cortical plate enveloping a diploic space containing bone trabeculae, marrow tissue and larger sinusoids. Hollow connections were frequently found in both the outer and inner cortical plates in both the untreated and the GBA-treated specimens. These connections contained marrow tissue that extended to the periosteum and the dura. The morphometric measurements revealed similar proportions of cortical, trabecular, and marrow areas in the right and left untreated bones. The area of the outer cortical plate was significantly larger than the area of the inner cortical plate. Bone density was similar in the right and left untreated and GBA-treated specimens, as was the frequency and width of hollow connections through the cortical bone plates. CONCLUSIONS: The symmetry between the left and right parietal bones concerning the large vessel topography and the histomorphometric parameters assessed was high. Hollow connections in the cortical plates were frequently found. The bilateral use of the parietal bones is suggested to be reliable in experimental GBA models regarding the blood supply and bone quality.

Animals↗
PubMed2006

Differential gene expression of bone anabolic factors and trabecular bone architectural changes in the proximal femoral shaft of primary hip osteoarthritis patients.

Previous studies have shown a generalised increase in bone mass in patients with osteoarthritis (OA). Using molecular histomorphometry, this study examined the in vivo expression of mRNA encoding bone anabolic factors and collagen type I genes (COL1A1, COL1A2) in human OA and non-OA bone. Bone samples were obtained from the intertrochanteric (IT) region of the proximal femur, a skeletal site distal to the active site of disease, from individuals with hip OA at joint replacement surgery and from autopsy controls. Semi-quantitative reverse transcription-polymerase chain reaction analysis revealed elevated mRNA expression levels of alkaline phosphatase (p < 0.002), osteocalcin (OCN) (p < 0.0001), osteopontin (p < 0.05), COL1A1 (p < 0.0001), and COL1A2 (p < 0.002) in OA bone compared to control, suggesting possible increases in osteoblastic biosynthetic activity and/or bone turnover at the IT region in OA. Interestingly, the ratio of COL1A1/COL1A2 mRNA was almost twofold greater in OA bone compared to control (p < 0.001), suggesting the potential presence of collagen type I homotrimer at the distal site. Insulin-like growth factor (IGF)-I, IGF-II, and transforming growth factor-beta1 mRNA levels were similar between OA and control bone. Bone histomorphometric analysis indicated that OA IT bone had increased surface density of bone (p < 0.0003), increased trabecular number (Tb.N) (p < 0.0003), and decreased trabecular separation (Tb.Sp) (p < 0.0001) compared to control bone. When the molecular and histomorphometric data were plotted, positive associations were observed in the controls for OCN/glyceraldehyde-3-phosphate dehydrogenase (GAPDH) versus bone tissue volume (r = 0.82, p < 0.0007) and OCN/GAPDH versus Tb.N (r = 0.56, p < 0.05) and a negative association was observed for OCN/GAPDH versus Tb.Sp (r = -0.64, p < 0.02). These relationships were not evident in trabecular bone from patients with OA, suggesting that bone regulatory processes leading to particular trabecular structures may be altered in this disease. The finding of differential gene expression, as well as architectural changes and differences in molecular histomorphometric associations between OA and controls, at a skeletal site distal to the active site of joint degeneration supports the concept of generalised involvement of bone in the pathogenesis of OA.

Aged↗
PubMed1999

[Biological effects of basic fibroblast growth factor (bFGF) and osteogenic protein-1 (OP-1/BMP-7) on bone marrow cells and development of cell-hybrid artificial bone].

In this study, the effects of bFGF and OP-1 on rat bone marrow cells and bone formation by the cultured bone marrow cells in porous hydroxyapatite (HA) in subcutaneous sites of syngeneic rats were investigated. The effects of bFGF and OP-1 on the proliferation and the differentiation of rat bone marrow cells were investigated by means of measurement of [3H] thymidine incorporation into DNA, ALP activity and bone nodule formation. This in vitro study showed that both bFGF and OP-1 increased [3H] thymidine incorporation, especially bFGF which stimulated it 3.5-fold at a dose of 30ng/ml. OP-1 stimulated ALP activity and bone nodule formation, whereas bFGF suppressed them. These data suggested that bFGF stimulates proliferation of rat bone marrow cells and OP-1 accelerates their differentiation. These growth factors were used to fabricate cell hybrid artificial bone, which consisted of the bone marrow cells. The ectopic bone formation was induced by the bone marrow cells cultured in HA, regardless of the treatment of these growth factors. However, the histological analysis revealed that the treatment with bFGF and/or OP-1 increased the area of new bone formation and accelerated the maturation of bone compared with the controls. The results suggested that the bone marrow cells cultured in HA three-dimensionally could be used clinically as a biomaterial. Furthermore, the use of bFGF and OP-1 to produce this cell-hybrid artificial bone increases its bone forming activity.

Animals↗
PubMed2006

[An experimental research on different temperature sintered bone as carrier of bone morphogenetic protein].

This study was conducted to find perfect temperature sintered bone as carrier of bone morphogenetic protein (BMP). The different temperature active sintered bones, which were made up of calcine bone and bone morphogenetic protein, were implanted into the defects of rabbit radius. Compared with the sintered bone of 600 degrees C, the sintered bone of 900 degrees C and 1200 degrees C could induce more pieces of bone formation and be replaced by new bone. There were more pieces of new bone formation in sintered bone of 900 degrees C and 1200 degrees C than those in sintered bone of 600 degrees C (P<0.05). There was no difference between the sintered bone of 900 degrees C and 1 200 degrees C (P>0.05). In comparison with the sintered bone of 600 degrees C and 1200 degrees C, the sintered bone of 900 degrees C may be the choicest carrier of bone morphogenetic protein.

Animals↗
PubMed1994

[The usefulness of early whole body bone scintigraphy in the detection of bone metastasis from prostatic cancer].

Early whole body bone scintigraphy was performed on 25 patients with prostatic cancer (15 cases with bone metastases and 10 cases without bone metastasis) to obtain anterior and posterior whole body images five minutes after administration of 99mTc-HMDP. The results were compared with the findings of routine bone scintigraphy after three hours, and the usefulness of the above method for the diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in which increased activity was found in the upper and lower lumbar vertebrae by routine bone scintigraphy but no abnormality was seen by early whole body bone scintigraphy, senile degenerative bone changes such as spondylosis deformans were observed by bone radiography. In cases with multiple bone metastases, abnormal multiple accumulations were found by both early whole body bone scintigraphy and routine bone scintigraphy. In addition, in cases showing super bone scan, high accumulation in the skeletal system had already been detected by early whole body bone scintigraphy. When the courses before and after treatment in nine cases of multiple bone metastases were passaged from the results of early whole body bone scintigraphy and from changes in tumor markers (prostatic specific antigen, gamma-semino protein and prostatic acid phosphatase), increased activity and the appearance of new hot spots as well as an increase in tumor markers were detected by early whole body scintigraphy in three of the four advanced cases, whereas decreased accumulations and a decrease in and normalization of tumor markers were observed in five improved cases.

Acid Phosphatase↗
PubMed1997

Neuropeptides in heterotopic bone induced by bone matrix in immunosuppressed rats.

The effects of cyclosporin A on the occurrence of neuroendocrine peptides in bone induced by demineralized allogeneic and xenogeneic bone matrix were studied in rats. Cyclosporin A enhanced bone induction in demineralized allogeneic bone matrix implants by 40% to 50% at 4 weeks, whereas there was no difference to the control group at 8 weeks. In demineralized xenogeneic bone matrix implants there was virtually no cartilage or bone formation at 4 weeks, but some bone and cartilage formation was seen at 8 weeks. In both cyclosporin A treated groups the net bone formation in demineralized xenogeneic bone matrix implants was increased four to five times at 4 weeks. Cyclosporin A treatment did not alter the temporal occurrence or distribution of neuropeptide containing nerve fibers in the bone induced by allogeneic bone matrix. Fibers containing substance P, calcitonin gene related peptide, neuropeptide Y, vasoactive intestinal peptide, and tyrosine hydroxylase were detected in the ossicles of cyclosporin A treated and control rats. In the xenogeneic bone matrix of the control group, no immunoreactive nerve fibers could be detected at 4 weeks, but at 8 weeks all five neuropeptides were detected. However, after cyclosporin A treatment immunoreactive nerve fibers could be seen at 4 weeks in the demineralized xenogeneic bone matrix implants. Thus, immunologic properties of the inductive matrix affect the yield of mineralized bone and the degree of innervation. Cyclosporin A decreases the immune response and enhances the formation of bone and the number of transmitter identified nerves in demineralized xenogeneic bone matrix induced ossicles.

Animals↗
PubMed2005

Involvement of endogenous bone morphogenetic protein (BMP) 2 and BMP6 in bone formation.

Although accumulated evidence has shown the bone anabolic effects of bone morphogenetic proteins (BMPs) that were exogenously applied in vitro and in vivo, the roles of endogenous BMPs during bone formation remain to be clarified. This study initially investigated expression patterns of BMPs in the mouse long bone and found that BMP2 and BMP6 were the main subtypes expressed in hypertrophic chondrocytes that induce endochondral bone formation. We then examined the involvement of the combination of these BMPs in bone formation in vivo by generating the compound-deficient mice (Bmp2+/-;Bmp6-/-). Under physiological conditions, these mice exhibited moderate growth retardation compared with the wild-type (WT) littermates during the observation period up to 52 weeks of age. Both the fetal and adult compound-deficient mice showed a reduction in the trabecular bone volume with suppressed bone formation, but normal bone resorption, whereas the single deficient mice (Bmp2+/- or Bmp6-/-) did not. When a fracture was created at the femoral midshaft and the bone healing was analyzed, the endochondral bone formation, but not intramembranous bone formation, was impaired by the compound deficiency. In the cultures of bone marrow cells, however, there was no difference in osteogenic differentiation between WT and compound-deficient cells in the presence or absence of the exogenous BMP2. We thus concluded that endogenous BMP2 and BMP6 cooperatively play pivotal roles in bone formation under both physiological and pathological conditions.

Animals↗
PubMed2003

Bisphosphonate incadronate inhibits maturation of ectopic bone induced by recombinant human bone morphogenetic protein 2.

To determine the effects of a bisphosphonate on the quality of bone morphogenetic protein-(BMP-) induced bone, incadronate was administered to rats in which subcutaneous ectopic bones were induced by recombinant human BMP-2. Incadronate (1 microg/kg/day) was administered to rats carrying the BMP-induced bones three times per week, from the 3rd to 7th week after BMP implantation (incadronate group). Aliquots of phosphate-buffered saline were administered in the same protocol without incadronate to the control group. During the 3rd, 4th, 7th, or 10th week, the BMP-induced bones were removed and observed by contact microradiography (CMR), H&E staining, enzyme histochemistry for tartrate-resistant acid phosphatase (TRAP), and immunohistochemistry for cathepsin K. By 3 weeks when administration of incadronate began, woven bones formed in the periphery of the BMP pellets and osteoclasts were attached to these bones. At 4 weeks, in both the incadronate and control groups, bone formation advanced inward. However, in the incadronate group, poorly calcified areas, corresponding to the remaining BMP pellets, were found in the middle areas of bone formation, whereas osteoclasts decreased when compared with those of the control group. During the 10 weeks, bone marrow was formed and the characteristics of lamellar bones, in which the lacunae of small osteocytes were regularly arranged, were noted in the control group. In contrast, the poorly calcified areas were still present up to 10 weeks in incadronate group in which the osteoclasts were also scarcer than in the control group. These findings suggested that osteoclast-mediated bone resorption was inhibited by incadronate administration, and that immature bones including the BMP pellets remained for a long time, indicating that the process of bone maturation was blocked. The possibility of using incadronate for the purpose of inhibiting osteoclastic bone resorption was confirmed, but further study is needed before clinical application.

Acid Phosphatase↗
PubMed2006

In vivo banking for vascularized autograft bone by intramuscular inoculation of recombinant human bone morphogenetic protein-2 and beta-tricalcium phosphate.

BACKGROUND: The gold standard of bone graft substitutes is vascularized autologous bone. Our strategy to acquire this bone substitute is using recombinant human bone morphogenetic protein (rhBMP)-2 with beta-tricalcium phosphate (TCP) as carrier to induce bone tissue in muscle and grafting as a muscle-pedicled bone flap. In our previous studies, morphologically controlled living bone was successfully induced in a rat muscular pedicle. Moreover, concurrent administration of bisphosphonate controlled the subsequent resorption of the induced bone. This study was conducted (1) to confirm that when the size of carrier is increased, the induced bone can form the same in the center as well as on the periphery of the carrier, and (2) to simulate in vivo banking for vascularized autograft bone. METHODS: In experiment 1200 microg rhBMP-2 and 10(-5) M bisphosphonate (Minodronate) were applied to a 1-cm-diameter sphere of beta-TCP. This sphere was then inoculated into rabbit quadriceps and harvested 5 weeks later (n = 3). In experiment 2, beta-TCP was generated as a one-third hollow cylinder with 4-mm outer radius, 2-mm inner radius, and 10-mm length. After 50 microg rhBMP-2 and 10(-5) M Minodronate were applied, this structure was then inoculated into rat quadriceps. Four weeks later, the induced bone was transplanted as a muscle-pedicled flap onto the adjacent femur and harvested after 4 and 8 weeks more (n = 3). RESULTS: In experiment 1, good bone formation was observed at the central as well as the peripheral region of the sphere. In experiment 2, good bone formation and bony union to the femur at both 4 and 8 weeks were detected on the X-ray film. The presence of new bone formation around the screw was observed. CONCLUSIONS: Transplantation of the beta-TCP carrier treated with rhBMP-2 and bisphosphonate into the muscular tissue may have clinical potential for in vivo banking for muscle-pedicled bone flaps.

Animals↗
PubMed2006

Bone marrow stromal cells upregulate expression of bone morphogenetic proteins 2 and 4, gap junction protein connexin-43 and synaptophysin after stroke in rats.

Bone morphogenetic proteins play a key role in astrocytic differentiation. Astrocytes express the gap junctional protein connexin-43, which permits exchange of small molecules in brain and enhances synaptic efficacy. Bone marrow stromal cells produce soluble factors including bone morphogenetic protein 2 and bone morphogenetic protein 4 (bone morphogenetic protein 2/4) in ischemic brain. Here, we tested whether intra-carotid infusion of bone marrow stromal cells promotes synaptophysin expression and neurological functional recovery after stroke in rats. Adult male Wistar rats were subjected to 2 h of right middle cerebral artery occlusion. Rats were treated with or without bone marrow stromal cells at 24 h after middle cerebral artery occlusion via intra-arterial injection (n=8/group). A battery of functional tests was performed. Immunostaining of 5-bromo-2-deoxyuridine, Ki67, bone morphogenetic protein 2/4, connexin-43, synaptophysin, glial fibrillary acidic protein, neuronal nuclear antigen, and double staining of 5-bromo-2-deoxyuridine/glial fibrillary acidic protein, 5-bromo-2-deoxyuridine/neuronal nuclear antigen, glial fibrillary acidic protein/bone morphogenetic protein 2/4 and glial fibrillary acidic protein/connexin-43 were employed. Rats treated with bone marrow stromal cells significantly (P<0.05) improved functional recovery compared with the controls. 5-Bromo-2-deoxyuridine and Ki67 positive cells in the ipsilateral subventricular zone were significantly (P<0.05) increased in bone marrow stromal cell treatment group compared with the controls, respectively. Administration of bone marrow stromal cells significantly (P<0.05) promoted the proliferating cell astrocytic differentiation, and increased bone morphogenetic protein 2/4, connexin-43 and synaptophysin expression in the ischemic boundary zone compared with the controls, respectively. Bone morphogenetic protein 2/4 expression correlated with the expression of connexin-43 (r=0.84, P<0.05) and connexin-43 expression correlated with the expression of synaptophysin (r=0.73, P<0.05) in the ischemic boundary zone, respectively. Administration of bone marrow stromal cells via an intra-carotid route increases endogenous brain bone morphogenetic protein 2/4 and connexin-43 expression in astrocytes and promotes synaptophysin expression, which may benefit functional recovery after stroke in rats.

Analysis of Variance↗
PubMed2004

Grafting of deproteinized bone particles inhibits bone resorption after maxillary sinus floor elevation.

OBJECTIVES: To evaluate the value of deproteinized bone particles on bone resorption in the augmented space after maxillary sinus floor elevation in rabbits. MATERIAL AND METHODS: A total of 20 rabbits underwent bilateral grafting, using blood clots (control group) and deproteinized bone particles (experimental group), and followed with histologic and histomorphometric analysis. RESULTS: Two weeks after grafting, the augmented space was almost completely obliterated by both newly formed bone and fibrous connective tissue in the control group. Some osteoclasts were found on the surface of newly formed bone, especially near the elevated sinus membrane. In the experimental group, newly formed bone was found along the elevated sinus membrane, the cortical wall of the augmented space, and the surface of deproteinized bone particles near the cortical wall. Some osteoclasts were found along the deproteinized bone particles and a few adhered to the surface of the newly formed bone. Eight to 10 weeks after implantation in the control group, most of the newly formed bone had been resorbed. In the experimental group, newly formed bone was found in most parts of the convex augmented space. Histomorphometrical analysis showed that the augmented height was significantly higher in the experimental group than in the control group at all evaluation times. Bone area was significantly higher in the experimental group than in the control group at 6, 8, and 10 weeks after implantation. The area of grafted deproteinized bone particles did not change significantly from 2 to 10 weeks. CONCLUSION: Slowly resorbed deproteinized bone particles contribute to stable augmentation of the maxillary sinus floor by inhibiting bone resorption.

Animals↗
PubMed1977

Decalcified bone as a substrate for osteogenesis. An appraisal of the interrelation of bone and marrow in combined grafts.

This paper examines the fate of decalcified allografts (homografts) of iliac cancellous bone impregnated with autologous red marrow and implanted intermuscularly into the anterior abdominal wall of rabbits. In contrast to the findings of Urist and other workers that cortical bone decalcified with hydrochloric acid (HCl) and then freeze-dried is inductive to new bone formation in various heterotopic sites, evidence is presented that iliac bone decalcified by HCl and grafted alone to a muscular site is itself very weakly inductive to bone formation. However, when combined with autologous bone marrow the HCl-decalcified bone provides a better substrate for bone formation by marrow cells than does either undecalcified iliac bone, or iliac bone decalcified with ethylene-diamine-tetra-acetic acid. The freezing or freeze-drying of decalcified bone does not affect new bone formation when implanted alone or with autologous marrow. The differences between the cortical and cancellous bone as inductive substrates for osteogenesis are discussed and the interrelationship of bone and marrow in combined bone grafts are re-evaluated.

Animals↗