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PubMed2002

[Repair of tibial defect with tissue-engineered bone graft and radionuclide bone imaging in goats].

OBJECTIVE: To observe the effect of tissue-engineered bone grafts in repairing large tibial defect in goats, and assess the value of radionuclide bone imaging in monitoring the therapeutic effect of this approach. METHODS: Tibial defects measuring 2 cm was artificially made in the left tibia of 27 normal goats that were subsequently divided into 3 groups (9 each) to undergo treatment with tissue-engineered bone grafts, artificial bone grafts or without any grafts (as control group) respectively. The tissue-engineered bone grafts contained bone marrow stroma cells (BMSCs) of the goats and coral hydroxyapatite (CHAP), while the artificial bone grafts were from CHAP only. After the operations, radionuclide bone imaging was used to monitor the therapeutic effects at 2, 4 and 8 postoperative weeks. RESULTS: The 99mTc-MDP uptake of the region of interest (ROI) and the target to non-target ratios (T/NT) of the control group did not indicate any process of revascularization or bone regeneration. An increasing tendency of the revascularization and bone regeneration, in contrast, was observed in goats receiving the artificial bone grafts, a tendency that was far more obvious in the goats with tissue-engineered bone grafts. CONCLUSION: Tissue-engineered bone graft is eligible in repairing large defect in the caprine tibia, and radionuclide bone imaging may accurately monitor the revascularization and bone regeneration after the bone graft implantation.

Animals↗
PubMed2002

Molecular evidence-based use of bone resorption-targeted therapy in prostate cancer patients at high risk for bone involvement.

BACKGROUND: To improve median survival of patients with prostate cancer that has metastasized to bone, we need to better understand the early events of the metastatic process in skeleton and develop molecular tools capable of detecting the early tumor cell dissemination into bones (micrometastasis stage). However, the initial phase of tumor cell dissemination into the bone marrow is promptly followed by the migration of tumor cells into bone matrix, which is a crucial step that signals the transformation of micrometastasis to macrometastasis stage and clinically evident metastasis. The migration of cancer cells into bone matrix requires the activation of local bone resorption. Such an event contributes to tumor cell hiding/ escaping from high immunologic surveillance of bone marrow cells. Within bone matrix, tumor cells are establishing plethoric cell-cell interactions with bone marrow-residing cells, ensuring their survival and growth. Recently, RT-PCR detections of tumor marker transcripts, such as PSA and PSMA mRNA performed in RNA extracts of peripheral blood nucleated cells and bone marrow biopsy, have enabled the stratification of patients with clinically localized prostate cancer being of high risk for extraprostatic disease and bone involvement. Therefore, it is conceivable that bisphosphonate blockade of bone resorption can inhibit the migration of tumor cells into bone matrix during the early phase of disease dissemination into bone marrow (micrometastasis stage). Consequently, assessment of the efficacy and efficiency of bisphosphonates to arrest the evolution of bone lesions in this particular clinical setting of patients with clinically localized prostate cancer and positive molecular staging status (high risk for bone involvement) is warranted.

Antineoplastic Agents↗
PubMed1990

Radioimmune imaging of bone marrow in patients with suspected bone metastases from primary breast cancer.

Radioimmune imaging of bone marrow was performed by technetium-99m- (99mTc) labeled antigranulocyte monoclonal antibody BW 250/183 (AGMoAb) scans in 32 patients with suspected bone metastases from primary breast cancer. AGMoAb scans showed bone marrow defects in 25/32 (78%) patients; bone invasion was subsequently confirmed in 23 (72%) patients. Conventional bone scans performed within the same week detected bone metastases in 17/32 (53%) patients (p less than 0.001). AGMoAb scans detected more sites indicating metastatic disease than bone scans in 12 of these 17 patients (71%). All patients with bone metastases in the axial skeleton had bone marrow defects at least at the sites of bone metastases. Of 15 patients with normal, or indicative of, benign disease bone scans, 8 patients (53%) presented with bone marrow defects in the AGMoAb scans. Bone invasion was confirmed in six of them. AGMoAb bone marrow scans provide a method for the early detection of bone metastatic invasion in patients with breast cancer and suspected bone metastases.

Antibodies, Monoclonal↗
PubMed1990

Biochemical markers of bone turnover for the clinical assessment of metabolic bone disease.

There is not yet an ideal marker of bone formation, but circulating BGP is the most satisfactory at present. New developments include the use of sheep BGP64 and human BGP85 as an immunogen and monoclonal antibodies, which may recognize fragments of BGP released during resorption. The specific measurement of bone alkaline phosphatase and the assay of procollagen fragments and of other noncollagenous bone-related proteins will allow a more precise assessment of the complex osteoblastic functions in normal and pathologic conditions. Finding a sensitive and specific marker of resorption is a challenge because all constituents of bone matrix are likely to be degraded into minute peptides during osteoclastic bone resorption. The measurement of pyridinium crosslinks and possibly of tartrate-resistant acid phosphate by a bone-specific monoclonal antibody are the most tangible improvements in this area. These markers need to be validated by comparison with data obtained by direct measurement of bone turnover on iliac crest biopsy. It should be remembered, however, that circulating markers reflect the overall activity of the whole skeleton, including the cortical, subcortical, and trabecular envelopes, which have different remodeling rates in normal and abnormal states. A circulating marker will not detect a specific defect of the cellular activity of one compartment of bone if the summated turnover of the skeleton is unchanged. Conversely, bone histomorphometry is limited to a small area of the trabecular envelope but allows detection of a specific defect at the cellular level. These differences should be kept in mind, as there is growing evidence that, for example, bone mass and bone turnover of osteoporotic patients before and during treatment vary in different appendicular/axial and cortical/trabecular compartments. Finally, a single marker might be valuable in some diseases and not in others (such as serum BGP in Paget's disease of bone). Despite these difficulties, significant advances have been made in the last few years in the bone marker field. In the future, the development of a battery of several bone-specific markers that indicate various aspects of the complex mechanisms of bone formation, resorption, and mineralization is likely to provide new tools for the diagnosis and management of bone diseases.

Biomarkers↗
PubMed2002

The bone lining cell: its role in cleaning Howship's lacunae and initiating bone formation.

In this study we investigated the role of bone lining cells in the coordination of bone resorption and formation. Ultrastructural analysis of mouse long bones and calvariae revealed that bone lining cells enwrap and subsequently digest collagen fibrils protruding from Howship's lacunae that are left by osteoclasts. By using selective proteinase inhibitors we show that this digestion depends on matrix metalloproteinases and, to some extent, on serine proteinases. Autoradiography revealed that after the bone lining cells have finished cleaning, they deposit a thin layer of a collagenous matrix along the Howship's lacuna, in close association with an osteopontin-rich cement line. Collagenous matrix deposition was detected only in completely cleaned pits. In bone from pycnodysostotic patients and cathepsin K-deficient mice, conditions in which osteoclastic bone matrix digestion is greatly inhibited, bone matrix leftovers proved to be degraded by bone lining cells, thus indicating that the bone lining cell "rescues" bone remodeling in these anomalies. We conclude that removal of bone collagen left by osteoclasts in Howship's lacunae is an obligatory step in the link between bone resorption and formation, and that bone lining cells and matrix metalloproteinases are essential in this process.

Animals↗
PubMed1993

Bone formation is not coupled to bone resorption in a site-specific manner in adult rats.

The trabecular bone of the secondary spongiosa of mature rats shows a coupling of bone formation to resorption. It has been clearly shown that 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 controversial. 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 to 2 years. A similar comparison was also made using bone from adult human iliac crest. We found that the trabecular bones of 16-week-old and 7-month-old rats exhibited a low percentage (7-11%) of crenated cement lines, which is opposite to the proportion (88%) we observed in human trabecular bone. In contrast, the surfaces of rat bone trabeculae showed a similar low proportion of crenated surface to human bone (rat 1.1-1.4% vs. 5% in humans). In older (2 years) rats, in which bones have ceased to grow in length, the percentage of cement lines that were crenated increased to 45%. These results imply that the major proportion of bone formation in the trabecular bone of growing rats occurs on non-resorbed surfaces.(ABSTRACT TRUNCATED AT 250 WORDS)

Aged↗
PubMed1988

Effects of a one-year administration of phosphate and intermittent calcitonin on bone-forming and bone-resorbing cells in involutional osteoporosis: a histomorphometric study.

The bone histomorphometric effects of intermittent phosphate and calcitonin therapy during 1 year were analyzed in 15 involutional osteoporotic patients. Phosphate was administered continuously (1.5 g/day) and calcitonin was injected during 5 days every third week (50 IU/day). The bone cell response was analyzed in two separate groups, according to the amount of trabecular bone present in the iliac bone biopsy: patients with trabecular bone volume (TBV) beyond the histomorphometric spontaneous fracture threshold (0.16 mm3/mm3) (group 1; 11 patients) and patients with TBV above this threshold (group 2; 4 patients). In group 1, the treatment significantly increased TBV from 0.113 +/- 0.025 to 0.156 +/- 0.046 mm3/mm3 by thickening the existing trabeculae rather than by creating new trabeculae; stimulation of bone formation rate (+ 50%) and significant reduction in active trabecular resorption surfaces (from 0.021 +/- 0.013 to 0.010 +/- 0.006 mm2/mm2; P less than .05) may have led to positive bone balance. In group 2, TBV was not changed because of the treatment's relative inefficiency for reducing the bone-resorbing cell activity, leading to likely persistent negative bone balance. Cortical thickness did not change in either group. This study confirms the positive effectiveness of continuous treatment with phosphate and intermittent calcitonin during 1 year on bone balance in involutional osteoporosis with low amount of bone. The lack of response in patients with normal amount of bone must be verified before raising the hypothesis of different bone cell activity and before anticipating the therapeutic response according to local bone mass besides bone remodeling status in osteoporosis.

Aged↗
PubMed2001

Bone disease after liver transplantation: a long-term prospective study of bone mass changes, hormonal status and histomorphometric characteristics.

After liver transplantation there is a high incidence of fractures, with important rates of bone loss during the first months. However, the long-term evolution of bone mass and metabolism parameters have been scarcely studied. In order to determine the incidence and risk factors involved in the development of skeletal fractures and to analyze the long-term evolution of bone mass, bone turnover and hormonal status after liver transplantation, a 3-year prospective study was performed in 45 patients following liver transplantation. Serum osteocalcin, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH D) and testosterone levels (men), and bone mass at the lumbar spine and femur were measured before and sequentially at different time points during 3 years. Spinal X-rays were obtained during the first year. Histomorphometric analysis of bone biopsies obtained in 24 patients within the first 12 hours after surgery and 6 months after transplantation was performed. Fifteen patients (33%) developed fractures after liver transplantation, and pre-transplant risk factors for fractures were age and low bone mass (odd's ratio for osteoporosis, 95% confidence interval: 5.69, 1.32-24.53). Serum PTH, osteocalcin, 25-OH D, testosterone and creatinine levels increased after transplantation. Moreover, PTH correlated with creatinine and osteocalcin values. Bone mass decreased during the first 6 months and reached baseline values at the lumbar spine the second year, with posterior significant recovery at the femoral neck. Long term evolution of femoral neck BMD correlated with PTH levels. Six months after transplantation bone histomorphometric data showed an increase in bone formation parameters. After liver transplantation there is a high incidence of fractures, specially in elderly patients and those with osteoporosis. Bone mass decreased in the short-term period and improved, initially at the lumbar spine and later at the femur, according to histomorphometric evidences of an increase in bone formation. The increase in creatinine values induces a secondary hyperparathyroidism that influences the changes in femoral bone mass. Treatment of osteoporosis shortly after liver transplantation may be important in the prevention of bone fractures, particularly in patients with low bone mass.

Adult↗
PubMed1996

Human osteoblasts survive and deposit new bone when human bone is implanted in SCID mouse.

We describe the first successful engraftment of viable human bone that maintains human osteoblast function and deposits new bone after implantation into pretreated SCID (Hu-bone-SCID) mice. The pretreatment consists of radiation before bone implantation and subsequent administration of antiasialo GM1 antisera every 7 days to deplete mouse macrophage and natural killer (NK) cell activity. The implanted bone samples were analyzed at various times up to 8 weeks. Comparison of pre- and post-implanted human specimens in untreated and pretreated SCID mice showed that while specimens underwent resorption and necrosis in untreated SCID mice, the structure of the implanted bone was preserved in the pretreated Hu-bone-SCID mice. In addition, histochemistry and histomorphometric analysis combined with tetracycline labeling showed that new bone formed in in the implants in the pretreated SCID mice. That the new bone resulted from the activity of the implanted human bone cells rather than from induction of differentiation of host mesenchymal cells into mouse osteoblasts was shown by immunohistochemical analysis with two different monoclonal antibodies (mAb), one mAb recognizing human HLA class II antigens and one recognizing human osteoblasts and osteocytes. Donor variability was observed in the implanted bone; however, bone from the same donor maintained its characteristics in all Hu-bone-SCID mice, and striking quantitative differences were seen in bone implanted from young (4-9 years) vs. adult (67-82 years) individuals. This model will be useful to investigate and compare endogenous osteoblast activity in different bone samples without the variables of isolating cells and examining them in vitro.

Aged↗
PubMed2004

Simvastatin treatment partially prevents ovariectomy-induced bone loss while increasing cortical bone formation.

Statins are commonly prescribed drugs that inhibit hepatic cholesterol synthesis and thereby reduce serum cholesterol concentrations. Some of the statins are thought to possess bone anabolic properties. Effects of statin on tibia, femur, and vertebral cortical and cancellous bone were studied in ovariectomized (OVX) rats. Sixty Wistar female rats, 4 months old, were allocated into four groups: baseline control, sham + placebo group, OVX + placebo, OVX + simvastatin. Simvastatin, 20 mg/kg, or placebo was given twice daily by a gastric tube for 3 months. The rats were labeled with tetracycline at day 11 and calcein at day 4 before sacrifice. Concerning cortical bone, the tibial diaphysis bending strength was increased by 8% and the periosteal bone formation rate (BFR) at the mid-diaphysis increased by twofold in the OVX + simvastatin group compared with the OVX + placebo group, in harmony with increased serum osteocalcin concentrations. Simvastatin did not affect the endocortical bone formation. Concerning cancellous bone, the cancellous bone volumes in the proximal tibia and vertebral body were reduced in both OVX groups, but the reduction was less in the OVX + simvastatin group compared with the OVX + placebo group. This reduction in cancellous bone loss is in agreement with the 36% decreased activity of serum tartrate-resistant-acid-phosphatase 5b (TRAP-5b), indicating decreased osteoclast activity in the OVX + simvastatin group compared with the OVX + placebo group. In conclusion, simvastatin induces a moderate increase in cortical bone formation at the periosteal bone surface. The new cortical bone exhibits a normal lamellar structure, and simvastatin seems to respect the regional pattern of bone formation, bone resorption, and drift; for example, no periosteal bone formation is observed in the vertebral canal. Furthermore, simvastatin reduces the loss of cancellous bone induced by ovariectomy.

Animals↗
PubMed2001

Ectopic bone formation in titanium mesh loaded with bone morphogenetic protein and coated with calcium phosphate.

The osteoinductive properties of porous titanium fiber mesh, with or without a calcium phosphate coating and loaded with recombinant human bone morphogenic protein-2 (rhBMP-2) or rhBMP-2 and native bovine BMP (S-300) were investigated in a rat ectopic assay model. A total of 112 calcium phosphate-coated and 112 noncoated porous titanium implants, either loaded with rhBMP-2 and S-300 or loaded with rhBMP-2 alone, were subcutaneously placed in 56 Wistar-King rats. The rats were killed 5, 10, 20, and 40 days postoperatively, and the implants were retrieved. Histologic analysis demonstrated that all growth factor and carrier combinations induced ectopic cartilage and bone formation at 5 and 10 days, respectively. At 20 days, bone formation increased and was characterized by trabecular bone and bone marrow-like tissue. At 40 days, more lamellar bone and hemopoietic bone marrow-like tissue were present. At both times, more bone had been formed in calcium phosphate-coated implants than in noncoated samples. Further, in rhBMP-2 and S-300-loaded specimens, bone formation was higher than in rhBMP-2 only-loaded specimens. In rhBMP-2 only-loaded specimens, bone formation was mainly localized inside the mesh material, whereas in specimens loaded with both rhBMP-2 and S-300, the bone was localized inside and surrounding the titanium mesh. The histological findings were confirmed by calcium content and alkaline phosphatase activity measurements. In addition, all specimens showed osteocalcin expression as early as 5 days postoperatively. Our results show that the combination of titanium mesh with BMPs can induce ectopic bone formation and that this bone formation seems to be similar to "enchondral" ossification. In addition, a thin calcium phosphate coating can have a beneficial effect on the bone-inducing properties of a scaffold material. Finally, rhBMP-2 and native BMP act synergistically in ectopic bone induction.

Alkaline Phosphatase↗
PubMed1998

Adhesive and bone resorptive activities of isolated osteoclasts from hen medullary bone.

In the present study, osteoclasts were isolated from hen medullary bones at the formative and resorptive phases. The cells were cultured on glass culture dishes and bone slices. After culturing, the adhesion activity of the isolated osteoclasts with the substrates was estimated with a light microscope, and the surfaces of the bone slices were observed with a scanning electron microscope. The results showed that the adhesion activity of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts is higher at the bone resorptive phase than at the bone formative phase, and this tendency in isolated osteoclasts was observed more frequently on the bone slices than on the glass culture dishes. Furthermore, scanning electron microscopy showed that the isolated osteoclasts in the bone resorptive phase adhered to the bone surface with developed-cytoplasmic projections and formed broad pits where collagen fibrils were exposed. On the other hand, isolated osteoclasts in the bone formative phase adhered to the bone slice with board-shaped cytoplasmic projections and did not form any pits. These results suggest that isolated osteoclasts in the bone resorptive phase have a high level of adhesion activity and actively resorb the bone, whereas isolated osteoclasts in the bone formative phase have a low level of adhesion activity and cease bone resorption. The procedure reported here is useful for studying the bone-resorptive mechanism of authentic osteoclasts.

Acid Phosphatase↗
PubMed1997

Quantification of biochemical markers of bone turnover by kinetic measures of bone formation and resorption in young healthy females.

The quantification of biochemical markers of bone formation and resorption with kinetic measures of bone turnover is an essential step in their validation. Some biochemical markers have been validated by quantification against formation and resorption rates measured by calcium kinetics in adults with bone disease. However, none has been validated in healthy individuals who are undergoing skeletal growth and bone consolidation. Therefore, we have measured biochemical markers of bone formation (serum osteocalcin [OC], bone-specific alkaline phosphatase [BAP], and total alkaline phosphatase [ALP]) and resorption (serum tartrate resistant acid phosphatase [TRAP], urinary cross-linked N teleopeptides of type I collagen/creatinine [NTx/Cr], and hydroxyproline/creatinine [OHP/Cr]) in healthy females aged 11-32 years (n = 31) after an overnight fast to determine their relationship with bone formation (Vo+) and bone resorption (Vo-) as measured by calcium kinetics and balance. All biochemical markers were highly intercorrelated (r > 0.6, p < 0.001) as were Vo+ and Vo- (r = 0.91, p < 0.001). Highly significant correlations were present between bone formation measured by calcium kinetics (Vo+) and serum levels of bone biochemical markers (OC, r = 0.82, p = 0.001; ALP, r = 0.92, p = 0.001; and BAP, r = 0.90, p = 0.001) and between bone resorption measured by calcium kinetics (Vo-) and fasting serum levels and urine creatinine ratios of biochemical markers (TRAP, r = 0.77, p < 0.001; OHP/Cr, r = 0.79, p < 0.001; and NTx/Cr, r = 0.70, p < 0.001). Thus, biochemical markers of bone formation and resorption can be used to predict calcium kinetic rates during skeletal growth and the early years of formation of peak bone mass, ages at which strategies to build peak bone mass are important. Biochemical markers of formation and resorption are equally useful in predicting either the bone formation rate or the resorption rate.

Acid Phosphatase↗
PubMed2004

Standardized data and relationship between bone growth and bone metabolism in female Göttingen minipigs.

Minipigs have been studied as a model of osteoporosis. However, little information is available regarding their bone physiology. We established standardized bone data and investigated the relationship between bone growth and bone metabolism in female minipigs. Blood and urine samples were obtained from 53 female Göttingen minipigs, 3-76 months of age, for measurement of bone biomarkers (i.e., BAP, OC, NTX, and DPD). The lumbar vertebra and femur were excised to determine the growth plate condition, bone length, bone mineral content (BMC), and bone mineral density (BMD). High levels of bone biomarkers were observed during the initial period after birth, decreasing thereafter with age. Bone biomarkers were confirmed to be highly correlated with age (R(2) > 0.7). The growth plates of the lumbar vertebra and the femur began to close at 21 and 25 months of age, respectively, and closed completely at 42 months of age. Bone length increased rapidly before growth plate closure, and reached a peak at 21 and 28 months of age in the lumbar vertebra and the femur, respectively. The levels of BMC and BMD increased rapidly before growth plate closure, and continued to increase slowly until 76 months of age. A high negative correlation (-0.855 < r < -0.711, p<0.001) was confirmed between the bone biomarkers and the bone measurement data. These results indicate that the bone turnover velocity is consistent with the bone growth velocity in female Göttingen minipigs.

Animals↗
PubMedDate not supplied

Histologic findings in sinus augmentation with autogenous bone chips versus a bovine bone substitute.

PURPOSE: The aim of this study was to compare a bovine bone substitute (Bio-Oss) to autogenous bone with respect to its value as a material for sinus augmentation. MATERIALS AND METHODS: In 10 beagle dogs 12 months of age, the 3 maxillary premolars were extracted on both sides. Six weeks later, 2 cavities of predefined size were produced in the region of the nasal cavity. The antral window was 25 mm long and had a vertical extension of 7 mm. Two Frialit-2 implants (3 x 8 mm) were placed in each bone defect (n = 20). Every implant was primarily stable because of fixation in native bone. In each maxilla, 1 bone defect was filled with autogenous bone harvested from the mandible and 1 was filled with Bio-Oss (material selected at random). The animals were sacrificed at 90 and 180 days, and histologic specimens were examined and the results subjected to statistical analysis by the Wilcoxon test for paired observations. RESULTS: No healing problems were observed. Histologically, after 90 days the volume of the augmentation showed a reduction of 14.6 +/- 4.4% within the Bio-Oss group and 3.8 +/- 2.5% in the group with autogenous bone. Bone-implant contact of 52.16 +/- 13.15% in the Bio-Oss group and 60.21 +/- 11.46% in the autogenous bone group was observed. At 180 days, the Bio-Oss group showed bony ingrowth of the substitute, whereas in the autogenous group a differentiation from original bone could no longer be made. The volume reduction was 16.5 +/- 8.67% in the Bio-Oss group and 39.8 +/- 16.14% in the autogenous group. Bone-implant contact of 63.43 +/- 19.56% in the Bio-Oss group and 42.22 +/- 12.80% in the autogenous bone group was measured. DISCUSSION AND CONCLUSION: The results indicated that because of the nonresorptive properties of the bone substitute Bio-Oss, regeneration of the defects is achievable. It was demonstrated that the bone substitute seemed to behave as a permanent implant. The volume of the area augmented by autogenous bone decreased over the observation period.

Alveolar Ridge Augmentation↗
PubMedDate not supplied

Utilization of autogenous bone, bioactive glasses, and calcium phosphate cement in surgical mandibular bone defects in Cebus apella monkeys.

PURPOSE: The purpose of the present study was to evaluate the histologic results of bone cavities that were surgically created in the mandibles of Cebus apella monkeys and filled with autogenous bone, PerioGlas, FillerBone, or Bone Source. MATERIALS AND METHODS: Surgical cavities 5 mm in diameter were prepared through both mandibular cortices in the mandibular angle region. The cavities were randomly filled, and the animals were divided into groups according to the material employed: Group 1 cavities were filled with autogenous corticocancellous bone; group 2 cavities were filled with calcium phosphate cement (BoneSource); and group 3 and group 4 cavities were filled with bioactive glass (FillerBone and PerioGlas, respectively). After 180 days the animals were sacrificed, and specimens were prepared following routine laboratory procedures for hematoxylin/eosin staining and histologic evaluation. RESULTS: The histologic analysis showed that autogenous bone allowed total repair of the bone defects; bioactive glasses (FillerBone and PerioGlas) allowed total repair of the defects with intimate contact of the remaining granules and newly formed bone; and the cavities filled with calcium phosphate cement (BoneSource) were generally filled by connective fibrous tissue, and the material was almost totally resorbed. DISCUSSION: The autogenous bone, FillerBone, and PerioGlas provided results similar to those in the current literature, showing that autogenous bone is the best choice for filling critical-size defects. Synthetic implanted materials demonstrated biocompatibility, but the bio-glasses demonstrated osteoconductive activity that did not occur with calcium phosphate (Bone-Source). CONCLUSION: According to the methodology used in this study, it can be concluded that the utilization of autogenous bone and bioactive glasses permitted the repair of surgically created critical-size defects by newly formed bone; the synthetic implanted materials demonstrated biocompatibility, and the bioactive glasses demonstrated osteoconductive activity. The PerioGlas was mostly resorbed and replaced by bone and the remaining granules were in close contact with bone; the FillerBone showed many granules in contact with the newly formed bone; BoneSource did not permit repair of the critical-size defects, and the defects were generally filled by connective fibrous tissue.

Animals↗
PubMed1988

A murine model of experimental metastasis to bone and bone marrow.

Bone is a common site of metastasis in human cancer. A major impediment to understanding the pathogenesis of bone metastasis has been the lack of an appropriate animal model. In this paper, we describe an animal model in which B16 melanoma cells injected in the left cardiac ventricle reproducibly colonize specific sites of the skeletal system of mice. Injection of 10(5) cells resulted in melanotic tumor colonies in most organs, including the skeletal system. Injection of 10(4) or fewer cells resulted in experimental metastasis almost entirely restricted to the skeletal system and ovary. In contrast, i.v. injection of 10(5) cells resulted in tumor colonies in the lung only. Left cardiac injection of 10(2) cells caused bone colonization, but the same number of cells injected i.v. did not colonize the lung. The number of bones with tumor colonies increased with increasing number of cells injected. Melanotic tumor colonies in the bone were characteristically distributed in the metaphysis of long bones and in the periphery of flat bones. Most animals developed paraplegia due to spinal cord compression by bony metastasis to the spine. Tumor colonization of bone occurred only in regions of bone containing hematopoietic bone marrow. This suggests that the injected tumor cells lodge, survive in the hematopoietic bone marrow environment, and grow to destroy adjacent bone. This experimental model of metastasis to bone will facilitate future studies of the pathophysiology and treatment of bone and bone marrow metastasis.

Animals↗
PubMed1982

[The influence of bone cement on the bone].

The investigation on the effects of bone cement on bone was undertaken in the present study. The experiments were conducted on the following 4 group of rabbits, A, B, C, and D. In group A the femoral medullary cavity was reamed, leaving the part of the endosteum of the cortex and bone marrow. In group B reaming of the medullary cavity was extensively performed to remove whole bone marrow and the part of endosteum of the cortex. The medullary spaces produced after the reaming both in group A and B were completely filled with bone cement. In group C, reaming was performed in the same manner as in group B, and the medullary space was kept empty as a control, furthermore, in order to compare the effects of the metal and bone cement on bone intermedullary nails were inserted into the medullary space after the same reaming as in group B. In comparison, the bone specimens were obtained from these 4 groups at intervals after the surgical treatments, the contact microradiographic and histopathological studies were carried out. The most important finding was the action of bone cement causing atrophy and degeneration of bone tissue over a prolonged period of time. The degree of these changes was found to vary depending upon the extent to which the medullary cavity was reamed prior to the introduction of bone cement. In the extensively reamed group, a considerable number of Howship's lacunae were observed along with cancellization of the cortex and, atrophy and degeneration of bone cells, even one year after the treatment. From this study, it was strongly indicated that the effects of bone cement on bone may be caused not only by the heat generated during polymerization, but also by some other factors responsible for the degeneration and atrophy of the bone over a long period of time.

Animals↗