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Early diagnosis for bone metastasis of breast cancer based on bone metabolism.

Bone metabolism was investigated in 152 patients with breast cancer comprising 109 without bone metastasis (negative group), 9 with suspicious bone metastasis (suspicious group) and 34 with bone metastasis (positive group). Bone scintigraphy had high sensitivity (100%) for diagnosis of bone metastasis, but its specificity was 79.8%. The levels of serum calcium corrected by serum albumin (CaC), ionized calcium (CaF) and serum alkaline phosphatase (ALP) were significantly higher in the positive group than in the negative one. Serum osteocalcin (OC) level was significantly higher in the positive and suspicious groups than in the negative group. The level of procollagen Type III N-peptide (PIIINP) was also higher in the positive group than in the other two groups. Microdensitometric parameters (MCI and sigma GS/D) showed significantly lower values in the positive group than in the negative and suspicious groups. Hormone receptors (ER and PgR) status and tumor markers (CEA, TPA, NCC-ST439 and CA15-3) were not related to the presence of bone metastasis. We conclude that repeated measurements of serum CaC, CaF, ALP, OC and PIIINP, and MCI and sigma GS/D are required to predict bone metastasis, and bone scintigraphy to confirm the site of lesion on the bone system and finally X-ray examination to make an exact diagnosis of pathological changes of the bone.

Adult↗

Bone regenerate formation in cortical bone during distraction lengthening. An experimental study.

The aim of this study was to delineate the pattern of bone regeneration from cortical bone segments during distraction lengthening. The lengthening procedure was applied for various periods through the Ilizarov system on the forearms of mature dogs. Bone was sectioned either by corticotomy, preserving the nutrient artery integrity, or by osteotomy. When an osteotomy was performed, the marrow cavity was in some cases plugged with either resorbable bone wax or nonresorbable material. Under distraction, both periosteal and medullary callus on either side of the gap gave rise to new bone trabeculae. The trabeculae on either side were oriented along the direction of distraction and progressively approached one another. This striated callus emerging from both sides was the most characteristic pattern of bone regeneration subsequent to distraction lengthening. Fusion was achieved approximately four weeks after the end of the lengthening period. Most of the new bone was formed by membranous ossification; some cartilaginous nodules developed. Corticalization of the bone trabeculae that had begun at three months was not fully achieved at five months after the lengthening period. There were no differences found in the pattern of bone healing and the amount of newly formed bone after corticotomy or osteotomy with or without resorbable bone wax plugging.

Animals↗

[Experimental study on secondary living bone graft--method of creating new donor by vascular bundle implantation to isolated bone].

The purpose of this study was to demonstrate the possibility of creating a new donor for a vascularized bone graft by a vascular bundle implantation to an isolated bone. Preliminary experiments on rats were performed preliminarily in order to investigate the revascularization of bone by a vascular bundle implantation and/or by implanting in muscular tissues (experiment-1). When a vascular bundle was implanted to the intramedullary cavity of an isolated bone and then the bone was implanted in muscular tissues, the isolated bone was more readily revascularized and revitalized than under other conditions. In experiment-2, the revascularized bone was transferred to the abdominal subcutaneous space on the vascular pedicle that was an implanted vascular bundle. Histologic and fluorochrome bone labeling studies showed that the revascularized bone was kept revitalized after the transfer. These results demonstrate that muscle and vascular bundle co-operated effectively in the revascularization of bone. Vascular bundle can also act as a pedicle for transferring the revascularized bone.

Animals↗

[Osteocalcin (or bone gla-protein), a new biological marker for studying bone pathology].

Osteocalcin, also called bone gla-protein, is a bone matrix protein synthetized specifically by osteoblasts. It circulates in blood where it can be assayed by the radioimmune method. We measured osteocalcin serum levels in 169 adult controls and 161 patients with different disseminated or localized bone diseases. The normal concentration of 6.2 +/- 0.2 ng/ml increases significantly with age. Serum osteocalcin levels are considerably increased in renal osteodystrophy (114 +/- 23 ng/ml) and to a lesser degree in primary hyperparathyroidism (15.9 +/- 2.8 ng/ml) and Paget's disease (11.4 +/- 0.9 ng/ml), all diseases characterized by increased bone turnover. High levels are also encountered in osteomalacia (9.7 +/- 0.9 ng/ml). Conversely, serum osteocalcin levels are significantly decreased in patients under long-term corticosteroid therapy (4.3 +/- 0.5 ng/ml); they remain normal in patients with bone myeloma and bone metastases under treatment. Finally, osteocalcin is normal in patients with osteoporosis, but its level reflects that of bone turnover as evaluated by iliac bone biopsy. The circulating osteocalcin therefore is the first specific and sensitive marker for bone turnover. Serum osteocalcin measurements make it possible to evaluate the osteoblastic bone formation without biopsy and should provide information on the effectiveness of drugs acting on the bone-forming process.

Adrenal Cortex Hormones↗

Purification and partial characterization of small proteoglycans I and II, bone sialoproteins I and II, and osteonectin from the mineral compartment of developing human bone.

Using nondegradative isolation procedures we purified and characterized five major noncollagenous proteins from developing human bone. Small bone proteoglycan I, Mr approximately 350,000 on sodium dodecyl sulfate (SDS), 4-20% gradient polyacrylamide gels has a different amino-terminal sequence of NH2-Asp-Glu-Glu-()-Gly-Ala-Asp-Thr and is not cross-reactive with the small bone proteoglycan II, Mr approximately 200,000 on SDS-gradient polyacrylamide gels. Bone proteoglycan II is 95% N terminally blocked and the small amount that can be sequenced has an amino-terminal sequence (NH2-Asp-Glu-Ala-()-Gly-Ile. . .) that is apparently similar but not identical to a small proteoglycan isolated by Brennan, M.J., Oldberg, A., Pierschbacher, M.D., and Ruoslahti, E. (1984) J. Biol. Chem. 259, 13742-13750 from human fetal placenta membrane. Two bone sialoproteins, each of which migrates at a Mr approximately 80,000 on SDS gels, have also been isolated. Bone sialoprotein I has an amino-terminal sequence of NH2-Ile-Pro-Val-Lys-Gln-Ala. . . which is different from that of bone sialoprotein II with an amino-terminal sequence of NH2-Phe-Ser-Met-Lys-Asn-Leu. . . The two bone sialoproteins do not cross-react on Western blot analysis. Human bone osteonectin contains a large number of cysteines, more than 90% of which appear to be in disulfide bonds. The N-terminal amino acid sequence of human bone osteonectin was nearly identical to bovine bone osteonectin and had many similarities to a protein found in mouse parietal endoderm (Mason, I.J., Taylor, A., Williams, J.G., Sage, H., and Hogan, B.L.M. (1986) EMBO J. 5, 1831-1837.

Amino Acids↗

[A study of bone metastasis of cervical carcinoma by bone scintigraphy].

In carrying out bone scintigraphy in 224 cases over the 5 years from June, 1978 to May, 1983 as a part of the post-treatment management of cervical carcinoma, we obtained the following findings concerning bone metastasis. Bone metastases were seen in 12.5% (28 cases) of the subjects, about 6% of the total post-treatment cases of cervical carcinoma in the corresponding period (466 cases). Bone metastases were seen in 9.3% (16/172) of post-operative cases, compared with 23.1% (12/52) of non-operative cases. Bone metastases were not seen in clinical stages Ia through IIa (49 cases) but were seen in IIb or higher stages. Bone metastasis rates by histological type, according to WHO classification, were 12.8% (26/203) in squamous cell carcinoma, 5.9% (1/17) in adenocarcinoma, and 25% (1/4) in adenosquamous carcinoma. Among the squamous cell carcinoma cases, small cell non-keratinizing type had the highest bone metastasis rate (p less than 0.05). Of 172 post-operative cases, 20.8% (11/53) of those with lymph node metastasis exhibited bone metastasis, higher than the 4.2% (5/119) in cases without lymph node metastasis. As to CPL classification, bone metastasis was seen more often in L type (18.8%) than C(0.0%) or P types (6.6%). Our risk classification of 168 cases demonstrated that bone metastasis was not seen in risk I group (74 cases), but was seen in 6.7% (1/17) of risk II group and in 19.0% (15/79) of risk III group. Twenty-eight cases with bone metastasis included 11 cases with local recurrence, 8 with pulmonary metastases, 4 with hepatic metastases and 4 with Virchow's lymph node metastases.(ABSTRACT TRUNCATED AT 250 WORDS)

Adenocarcinoma↗

Chemosterilized autolyzed antigen-extracted allogeneic (AAA) bone matrix gelatin for repair of defects from excision of benign bone tumors: a preliminary report.

In a series of 33 bone graft operations, antigen-extracted, autolyzed, allogeneic (AAA) bone matrix gelatin was substituted for autologous bone. The period of follow-up was 2.0 to 3.5 years. AAA bone gelatin was resorbed more rapidly than whole bone. AAA bone gelatin was replaced by new bone in the same intervals of time as observed with autologous bone. In treatment of bone tumors with AA bone gelatin, the results of the operation depend upon the nature of the pathologic processes in the host bed. In normal host bed, tight contact between implant and recipient bone is essential for success. The overall results of a preliminary study of 33 cases of 91% successful.

Antigens↗

Bone morphogenetic protein 2 accelerates osteointegration and remodelling of solvent-dehydrated bone substitutes.

INTRODUCTION: lt was the purpose of this study to investigate how bone morphogenetic protein 2 (BMP-2) influences remodelling and the biomechanics of solvent-dehydrated bone in the long run. Furthermore, the early influence of this growth factor on the substitute was investigated. MATERIALS AND METHODS: Using a weight-bearing animal model, solvent-dehydrated bone was implanted in the tibial head of merino sheep ( n=12) after being loaded with BMP-2 (100 microg/100 microl). At 4 weeks ( n=6) and 9 months ( n=6) after surgery, histomorphological, histomorphometrical and biomechanical investigations were performed. RESULTS: At 9 months after implantation of BMP-2-loaded specimens, the bone per tissue volume was high, with levels above those of physiological cancellous bone. The amount of remaining solvent-dehydrated bone was markedly decreased, and in contrast, the amount of newly formed bone was extremely high. The specimen degradation had already occurred within the first 4 weeks after implantation, showing no further impact throughout the 9-month period. Biomechanical investigations at 9 months after implantation demonstrated a yield strength which achieved levels at least equivalent to physiological cancellous bone. BMP-2 showed no significant impact on the biomechanical properties after 4 weeks, compared to specimens prior to implantation. CONCLUSION: BMP-2 predominantly has an impact on the early implant degradation as well as bone formation, which leads to an almost completed bone remodelling of the solvent-dehydrated specimen within the study period of 9 months.

Animals↗

Relationships between calcium and phosphorus homeostasis, parathyroid hormone levels, bone aluminum, and bone histomorphometry in patients on maintenance hemodialysis.

Serum biochemistry related to calcium and phosphorus homeostasis and parathyroid function was studied together with bone histomorphometry after double-labeling with tetracycline and staining for aluminum in 17 patients without symptoms of bone disease, treated with maintenance hemodialysis for at least 6 months. A close correlation was found between the serum level of parathyroid hormone (PTH) and bone resorption surfaces and bone formation rates, both at tissue and basic multicellular unit (BMU) levels. The patients could be divided into a high turnover group with a normal mineralization process and a low turnover group with markedly defective mineralization. The second group was further characterized by lower PTH and higher fractional aluminum-stained trabecular bone surfaces. For the whole patient material, the fractional aluminum-stained surfaces related inversely to tetracycline-labeled surfaces and to bone formation rates at both BMU and tissue levels, but not to the time on dialysis or to the cumulative ingested amount of aluminum hydroxide. The data provide evidence that PTH or PTH-related factors, besides activating bone remodeling, directly enhance bone formation in dialysis patients and that aluminum incorporation into bone is associated with a progressive disturbance of bone mineralization.

Adult↗

Dual growth factor delivery and controlled scaffold degradation enhance in vivo bone formation by transplanted bone marrow stromal cells.

Supraphysiological concentrations of exogenous growth factors are typically required to obtain bone regeneration, and it is unclear why lower levels are not effective. We hypothesized that delivery of bone progenitor cells along with appropriate combinations of growth factors and scaffold characteristics would allow physiological doses of proteins to be used for therapeutic bone regeneration. We tested this hypothesis by measuring bone formation by rat bone marrow stromal cells (BMSCs) transplanted ectopically in SCID mice using alginate hydrogels. The alginate was gamma-irradiated to vary the degradation rate and then covalently modified with RGD-containing peptides to control cell behavior. In the same delivery vehicle, we incorporated bone morphogenetic protein-2 (BMP2) and transforming growth factor-beta3 (TGF-beta3), either individually or in combination. Individual delivery of BMP2 or TGF-beta3 resulted in negligible bone tissue formation up to 22 weeks, regardless of the implant degradation rate. In contrast, when growth factors were delivered together from readily degradable hydrogels, there was significant bone formation by the transplanted BMSCs as early as 6 weeks after implantation. Furthermore, bone formation, which appeared to occur by endochondral ossification, was achieved with the dual growth factor condition at protein concentrations that were more than an order of magnitude less than those reported previously to be necessary for bone formation. These data demonstrate that appropriate combinations of soluble and biomaterial-mediated regulatory signals in cell-based tissue engineering systems can result in both more efficient and more effective tissue regeneration.

Animals↗

Effect of bone chip orientation on quantitative estimates of changes in bone mass using digital subtraction radiography.

OBJECTIVES: To assess the effect of the orientation of arbitrarily shaped bone chips on the correlation between radiographic estimates of bone loss and true mineral loss using digital subtraction radiography. METHODS: Twenty arbitrarily shaped bone chips (dry weight 1-10 mg) were placed individually on the superior lingual aspect of the interdental alveolar bone of a dry dentate hemi-mandible. After acquiring the first baseline image, each chip was rotated 90 degrees and a second radiograph was captured. Follow-up images were created without the bone chips and after rotating the mandible 0, 1, 2, 4, and 6 degrees around a vertical axis. Aluminum step tablet intensities were used to normalize image intensities for each image pair. Follow-up images were registered and geometrically standardized using projective standardization. Bone chips were dry ashed and analyzed for calcium content using atomic absorption. RESULTS: No significant difference was found between the radiographic estimates of bone loss from the different bone chip orientations (Wilcoxon: P > 0.05). The correlation between the two series of estimates for all rotations was 0.93 (Spearman: P < 0.05). Linear regression analysis indicated that both correlates did not differ appreciably ( and ). CONCLUSION: It is concluded that the spatial orientation of arbitrarily shaped bone chips does not have a significant impact on quantitative estimates of changes in bone mass in digital subtraction radiography. These results were obtained in the presence of irreversible projection errors of up to six degrees and after application of projective standardization for image reconstruction and image registration.

Alveolar Process↗

A 1-year prospective study on the relationship between physical activity, markers of bone metabolism, and bone acquisition in peripubertal girls.

We conducted a 1-yr prospective study to evaluate the association between physical activity and biochemical markers of bone formation and resorption with bone mineral acquisition in 155 peripubertal Caucasian girls (51 gymnasts, 50 runners, and 54 nonathletic controls). The bone mineral density (BMD) of the femoral neck, the greater trochanter, and the lumbar spine were measured by dual energy x-ray absorptiometry. Serum biochemical markers of bone formation (osteocalcin, bone-specific alkaline phosphatase, amino-terminal propeptide of type I procollagen) and bone resorption (degradation product of C-terminal telopeptide of type I collagen) were measured. The 1-yr increase in BMD (adjusted for age, height, Tanner stage, BMD at baseline, and increases in height and weight) of the femoral neck was 0.037 g/cm2 x yr [95% confidence interval (CI), 0.019-0.051 g/cm2 x yr), and that of the greater trochanter was 0.020 g/cm2 x yr (95% CI, 0.003-0.039 g/cm2 x yr) greater in gymnasts than in controls. The corresponding figures for gymnasts compared with runners were 0.038 g/cm2 x yr (95% CI, 0.009-0.041 g/cm2 x yr) and 0.033 g/cm2 x yr (95% CI, 0.006 to 0.043 g/cm2 x yr). The figures for the lumbar spine did not differ significantly between study groups. The baseline serum concentrations of formation markers and resorption marker accounted for 2.3-12.8% (P < 0.05) of the variation in the 1-yr increase in BMD at the femoral neck and lumbar spine. However, there was no significant difference between the levels of adjusted baseline bone turnover markers of the gymnasts, runners, and controls. The present data add considerable support to the argument that high impact mechanical loading is extremely important and beneficial for the acquisition of BMD of the hip during peripubertal years. Our results indicate also that a high rate of bone turnover, reflected as elevated bone markers, is only weakly associated with the 1-yr bone gain in peripubertal girls.

Adolescent↗

Does bone mass equate with bone health? An argument for the negative.

This article argues that diagnosing osteopenias and osteoporoses by bone mass Z-scores, and viewing disorders detected in that way as diseases, fostered a belief that those scores evaluate whole-bone strength and bone health equally well (here, mass has its meaning in absorptiometry, not in physics). However, load-bearing bones normally adapt their strength to the past and present voluntary loads on them in ways that make strong muscles make strong bones, and make persistently weak muscles make weak bones. The resulting adaptations also make bones strong enough to keep voluntary mechanical usage from fracturing them. Such observations suggest a new criterion for a bone's health that would depend on the relationship among its strength, the size of the voluntary loads it carries, and any spontaneous fractures caused by those loads. Such a relationship could indicate a bone"s health independently of its mass. For example, mouse and horse femurs differ in strength more than 1000-fold, but they could be equally healthy if they were to satisfy that criterion in the animals from which they come. That idea would distinguish abnormal in a strictly statistical sense (which T- and Z-scores would evaluate) from unhealthy in the sense of both abnormal and diseased (which the above relationship would evaluate). Thus, a bone with a negative Z-score could still be healthy if voluntary loads do not fracture it. These ideas and some of their implications question some long-held views. This article presents the ideas, evidence they stand on, and some of their implications.

Absorptiometry, Photon↗

Osteogenesis after bone and bone marrow transplantation. Studies of cellular behaviour using combined myelo-osseous grafts in the subscorbutic guinea pig.

In order to study factors influencing osteogenesis after bone and bone marrow transplantation, we have caused guinea pigs to become scorbutic, and looked at the cell morphology at sites of bone formation. We had previously studied normal guinea pigs and found that autologous marrow in intermuscular implants was associated with bone production by the ninth day, regardless of the type of stored allogeneic bone transplanted with it. In subscorbutic guinea pigs, using identical implants, bone did not appear within the first 13 days, and the cell population around the implants was different. These experiments support the dominant role of bone marrow cells in osteogenesis and cast further doubt on the primary role of devitalised bone as an inducer of bone formation. Interference with cell function by deprivation of a single essential molecule, Vitamin C, produces great change in the ability of cells to synthesise bone, or pre-osseous matrix.

Animals↗

Metabolic consequences of bone turnover in Paget's disease of bone.

High rates of bone resorption, bone formation, and marrow fibrosis are characteristic of Paget's disease of bone. This excessive bone turnover is reflected by increased fluxes of calcium ions out of and into the skeleton. The rates of these fluxes are highly geared to each other such that calcium balances are close to zero in the absence of fracture or significant immobilization. An increased turnover of bone matrix is also evident by increased urinary excretion of collagen breakdown products (oligopeptides of hydroxyproline, hydroxylysine, and hydroxylysine glycosides) as well as products (peptides of higher molecular weight) related to collagen synthesis. Increased circulatory levels of procollagen extension fragments reflect increased synthesis of Type I collagen (bone matrix) and Type III collagen (marrow fibrosis). Increased levels of bone gamma-carboxyglutamic acid-protein presumably reflect primarily bone matrix synthesis but bone resorption as well. When bone resorption is suppressed pharmacologically, the abnormal levels of these markers of matrix turnover and osteoblastic activity (alkaline phosphatase) also decrease, presumably as a result of coupling of resorption and formation.

Bone Development↗

Texture analysis of X-ray radiographs of iliac bone is correlated with bone micro-CT.

INTRODUCTION: Alteration of bone trabecular architecture is a predictor of fracture risk in osteoporosis. Until now, microarchitecture can only be measured on a bone biopsy, thus limiting microarchitecture analysis in routine clinical practice for osteoporosis. Texture analysis on X-ray images has been advocated to be a suitable means to assess two-dimensional (2-D) microarchitecture in the research field. But little is known about the relationships between three-dimensional (3-D) architecture and texture analysis, particularly in clinical practice. The purposes of the study were: (1) to explore the relationship between 3-D histomorphometric parameters and 2-D texture analysis, and (2) to see if cortical assessment may influence results. METHODS: In this study, the anterosuperior part of the iliac bone was removed from 24 cadavers. Large samples were prepared and comprised of the crest and a strip of bone approximately 3 cm wide and 5 cm long. These large specimens were used in order to preserve bone architecture; they also corresponded to the location used by histomorphometrists for the diagnosis of metabolic bone diseases on iliac crest biopsies. Bone samples were examined with a microcomputed tomograph for 3-D microarchitecture [BV/TV, C.BV/C.TV, Tb.P(f), structure model index (SMI), Tb.Th, Tb.N, Tb.Sp]. Texture analysis was done by several methods (skeletonization, run lengths, fractal techniques) from X-ray projection images. No correlation was found between bone mass parameters (BV/TV and C.BV/C.TV, which take into account both cortical and trabecular bone) and texture parameters. RESULTS: However, when specific descriptors of trabecular bone microarchitecture were used, several relationships with texture parameters were found [(Tb.N)/BOUND, r=0.628;/VGLN, r=0.596;/Fractal D, r=0.569]. CONCLUSION: When multiple correlations were used, the correlation coefficients were markedly improved with trabecular characteristics. X-ray texture analysis seemed to be a suitable approach for 2-D bone microarchitecture assessment. Furthermore, there is a good correlation between texture analysis of X-ray radiographs and 3-D bone microarchitecture assessed by microcomputed tomography.

Cadaver↗

Soft-tissue haemangioma and periosteal new bone formation on the neighbouring bone.

Deeply situated soft-tissue haemangioma sometimes causes periosteal new bone formation on the neighbouring bone. The purpose of this study was to elucidate the aetiological factors for this phenomenon. We studied 25 patients with soft-tissue haemangioma on whom plain radiographs and computed tomography (CT) and/or magnetic resonance imaging (MRI) examinations were performed. We examined the presence or absence of periosteal new bone formation, haemangioma-bone distance, size of haemangioma and pain. Periosteal new bone formation was seen in 12 of 25 patients. In these 12 patients, the haemangioma was adjacent to the bone in 11 patients, while the haemangioma-bone distance was 4 mm in the other patient. In the remaining 13 patients who had no periosteal new bone formation, the haemangioma-bone distance was 5-27 mm. Pain in the former group was stronger than that in the latter group, the difference being statistically significant. There was no statistically significant difference in size of haemangioma between the two groups. Therefore, the main factor that induces periosteal new bone formation on the neighbouring bone was not the size of haemangioma, but the distance between the haemangioma and the bone.

Adolescent↗

The effects of bovine trabecular bone matrix particulates on cortical bone repair.

This paper reports the effects of a synthetic bone substitute and bone allograft on cortical bone repair in an experimental model. To test the hypothesis that bovine trabecular bone matrix, BBM, can enhance the repair rate of cortical bone, osteotomies were created in the rabbit fibula and filled with either allograft or BBM particulates or left empty as controls. At five weeks post-surgery, mechanical tests and histological evaluations were performed. No significant differences were observed in the mechanical properties of the healing bone in the three animal groups (n=6). Histologically, the medullary cavity was obstructed and the cross-sectional area ratio of the osteotomies to intact bone was approximately 3 : 1. Highly significant area differences were observed between the intact bone group and both the BBM and the allograft groups (p< 0.001). At the junction between the original bone and the newly formed bone, both woven and lamellar bone microstructures were prevalent. However, in the BBM filled defects, the woven bone microstructure was not ostentatious. It is concluded that failure to demonstrate significantly differences between the treatments were due to the small sample sizes and or the efficacy of the tensile analysis.

Journal Article↗