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Stiffening effects of cortical bone on vertebral cancellous bone in situ.

STUDY DESIGN: This study tested a theory about vertebral cancellous bone stiffness by performing experimental tests and comparing the results with the theoretical predictions. OBJECTIVES: To test experimentally a theoretical prediction that vertebral cancellous bone appears stiffer than would be expected from isolated tests because of the constraining effects of the cortical bone, to measure the magnitude of this strengthening effect and its dependency on tissue composition and density. SUMMARY OF BACKGROUND DATA: Vertebral bodies are composed mainly of cancellous bone surrounded by a thin shell of much stronger cortical bone. Little is known of the ways in which these two materials function synergistically to produce strong but light structures and why sometimes extensive damage to the cancellous bone has apparently little outward effect on vertebral body strength. METHODS: Cancellous bone from 45 lumbar vertebrae from a homogeneous group of pigs was tested in compression both in situ in the vertebral body and as an excised cylinder. The density and composition of the bone were then measured and correlation tested with both of the stiffness measurements. RESULTS: The cancellous bone in situ appears much stiffer than when isolated by a factor of about 4 (range, 1.6-12). No correlation was found between stiffness, either in situ or in isolation, and density, although density is predicted entirely by the volume fractions of water, organic, and mineral phases. CONCLUSIONS: Combining low density cancellous bone with stiffer, more dense cortical bone leads to a lightweight structure that is much stronger than might be expected from the isolated properties of its components.

Animals↗

Marked disproportionality in bone size and mineral, and distinct abnormalities in bone markers and calcitropic hormones in adult turner syndrome: a cross-sectional study.

Most women with Turner syndrome (TS) have no gonadal activity and thus lack estrogen. Bone mineral density (BMD) is often reduced, leading to an increased risk of osteoporosis and fractures. However, growth retardation with reduced final height and other endocrine disturbances may compromise interpretation of skeletal measurements. The aim of the present study was to explore skeletal findings, bone metabolism, and calcium homeostasis in TS. Sixty women with TS (age, 37 +/- 9 yr) and 181 normal age-matched female controls were studied. Bone area (A; square centimeters), bone mineral content (BMC; grams), area-adjusted BMD (aBMD; grams/square centimeter), and volumetric BMD (vBMD; grams/cubic centimeter) were measured at lumbar spine, femoral neck, and forearm using dual energy x-ray absorptiometry. Twenty-eight percent had osteopenia, and 23% had osteoporosis, according to World Health Organization criteria. At the lumbar spine, A, BMC, aBMD, and vBMD were reduced by 18, 27, 11, and 6%, respectively; at the femoral neck, A, BMC, and aBMD were reduced by 2, 10, and 8%, respectively, whereas the 9% reduction in vBMD was insignificant (P = 0.07); and in the forearm, A, BMC, and aBMD were reduced by 53, 55, and 9%, respectively. Bone markers indicated an enhanced bone resorption (21 and 23% increase in C-terminal and N-terminal cross-linking telopeptides of type I collagen/creatinine, respectively) with unchanged (osteocalcin, procollagen I N-terminal propeptide) or reduced (54% reduction in bone alkaline phosphatase) bone formation. Plasma levels of calcium and 25-hydroxyvitamin D (26%) were reduced, and PTH levels increased (74%) in TS. IGF-I (30%), IGF binding protein 3 (18%), testosterone (50%), and SHBG (40%) were reduced in TS. In summary, A, BMC, and aBMD were found to be universally reduced in TS, whereas vBMD was slightly reduced in the spine. Increased resorption of bone was present, with normal or blunted bone formation, suggesting uncoupling or imbalance in bone remodeling. Skeletal changes may be induced by chromosome abnormalities or by secondary endocrine or metabolic changes related to a relative estrogen deficiency, testosterone deficiency, reduced IGF-I, low vitamin D status, and secondary hyperparathyroidism.

Adult↗

Bone repair induced by bone morphogenetic protein in ulnar defects in dogs.

In dogs, resection of a length of the ulna equal to twice the diameter of the mid-shaft leaves a defect which consistently fails to unite. In response to an implant of 100 mg of bovine bone morphogenetic protein (BMP), the defect becomes filled by callus consisting of fibrocartilage, cartilage and woven bone within four weeks. The cartilage is resorbed and replaced by new bone in four to eight weeks. Woven bone is then resorbed, colonised by bone marrow cells and remodelled into lamellar bone. Union of the defect is produced by 12 weeks. Control defects filled with autogeneic cortical bone chips unite after the same period. In regeneration induced by bone morphogenetic protein (BMP) and in repair enhanced by bone graft, union depends upon the proliferation of cells within and around the bone ends. Our working hypothesis is that BMP induces the differentiation of perivascular connective tissue cells into chondroblasts and osteoprogenitor cells and thereby augments the process of bone regeneration from the cells already present in the endosteum and periosteum.

Animals↗

Effect of resistance exercise training on bone formation and resorption in young male subjects assessed by biomarkers of bone metabolism.

We studied the effects of high intensity resistance exercise training on bone metabolism in 17 young adult Oriental males (23-31 years) by measuring sensitive biomarkers of bone formation and resorption. The subjects were assigned to a training group and a sedentary group. The training group followed a weight training program three times per week for 4 months. In the training group, serum osteocalcin concentration and serum bone-specific alkaline phosphatase activity were significantly increased within the first month after the beginning of resistance exercise training, and the elevated levels remained throughout the training period, while there was no significant change in plasma procollagen type-I C-terminal concentration. Urinary deoxypyridinoline excretion was transiently suppressed and returned to the initial value but was never stimulated during the 4 months. These results suggest that the resistance exercise training enhanced bone formation without prior bone resorption. In the sedentary group, there was no significant difference in bone metabolic markers except plasma procollagen type-I C-terminal, which continuously decreased during the experimental period. There were no significant changes in total and regional bone mineral density in either group. In conclusion, (1) resistance exercise training increased markers of bone formation, while it transiently suppressed a marker of bone resorption, and (2) such adaptive changes of bone metabolism to resistance exercise training occurred during the early period of the training, before changes in bone density were observable through densitometry.

Adult↗

The role of whole-body bone scanning and clinical factors in detecting bone metastases in patients with non-small cell lung cancer.

STUDY OBJECTIVES: Correct detection of bone metastases in patients with non-small cell lung cancer (NSCLC) is crucial for prognosis and selection of an appropriate treatment regimen. The aim of this study was to investigate the role of whole-body bone scanning (WBBS) and clinical factors in detecting bone metastases in NSCLC. DESIGN AND PATIENTS: One hundred twenty-five patients with a diagnosis made between 1998 and 2002 were recruited (squamous cell carcinoma, 54.4%; adenocarcinoma, 32.8%; non-small cell carcinoma, 8.8%; large cell carcinoma, 4%). Clinical factors suggesting bone metastasis (skeletal pain, elevated alkaline phosphatase, hypercalcemia) were evaluated. WBBS was performed in all patients, and additional MRI was ordered in 10 patients because of discordance between clinical factors and WBBS findings. MEASUREMENTS AND RESULTS: Bone metastases were detected in 53% (n = 21) of 39 clinical factor-positive patients, 5.8% (n = 5) of 86 clinical factor-negative patients, and 20.8% of total patients. The existence of bone-specific clinical factors as indicators of metastasis presented 53.8% positive predictive value (PPV), 94.2% negative predictive value (NPV), and 81.6% accuracy. However, the findings of WBBS showed 73.5% PPV, 97.8% NPV, and 91.2% accuracy. Adenocarcinoma was the most common cell type found in patients with bone metastasis (39%). The routine bone scanning prevented two futile thoracotomies (8%) in 25 patients with apparently operable lung cancer. CONCLUSIONS: In spite of the high NPV of the bone-specific clinical factors and the high value obtained in the false-positive findings in the bone scan, the present study indicates that in patients for whom surgical therapy is an option, preoperative staging using WBBS can be helpful to avoid misstaging due to asymptomatic bone metastases.

Adult↗

A comparison of ePTFE membranes alone or in combination with platelet-derived growth factors and insulin-like growth factor-I or demineralized freeze-dried bone in promoting bone formation around immediate extraction socket implants.

The purpose of this study was to compare bone promotion around implants which were augmented with ePTFE membranes alone or in combination with cortical demineralized freeze-dried bone (DFDB) or the combination of platelet derived growth factor-BB (PDGF) and insulin like growth factor I (PDGF/IGF-I). Membranes were placed over titanium implants which had been inserted into fresh extraction sockets with large buccal dehiscences. Twenty-four implants were placed in 4 dogs. At 18 weeks clinical bone height measurements were taken, the animals were sacrificed, and all specimens retrieved for histologic evaluation. Clinically, a significant gain in bone levels was present in both the ePTFE membrane alone group (P < 0.005) and PTFE plus PDGF/IGF-I group (P < 0.01), but not in the PTFE plus DFDB group. Results from histometric measurements revealed an approximately 2-fold increase in the percentage of implant surface in contact with bone, area of bone adjacent to the implant surface, and in the total length of the implant surface in contact with bone in the dehiscence defects treated with ePTFE plus PDGF/IGF-I compared to the defects receiving ePTFE membranes alone (each P < 0.05). The response to the DFDB was highly variable and it did not significantly improve the efficacy of the PTFE membranes for any parameter measured. The distance from the outer surface of the new bone to the implant surface was statistically significant for ePTFE membranes alone and membranes plus PDGF/IGF-I. The results demonstrated that clinically, ePTFE membranes alone or ePTFE membranes with PDGF/IGF-I were equally effective in promoting bone growth around the implants. Histologic measurements demonstrated that sites treated with ePTFE membranes plus PDGF/IGF-I had the highest bone density compared with sites which received ePTFE membranes alone or with ePTFE membranes and DFDB. The results of this study question the use of DFDB and support the use of ePTFE membranes alone or with PDG-F-BB/IGF-I as potential methods of promoting bone formation around dental implants.

Alveolar Bone Loss↗

Thermal stability of bone collagen as an indicator of bone turnover in gonadectomized and multiparous rats.

Previous findings indicate that the thermal stability of bone collagen is related to age. In this study, collagen from rat bone with reported different turnover rates was investigated. Cortical and trabecular bone from femur were obtained from intact, ovariectomized, orchidectomized and multiparous breeder rats. Thermal stabilities of fibrillar collagen in decalcified bone matrix and molecular collagen obtained by pepsin treatment were measured as shrinkage (Ts) and 'melting' temperature (Tm), respectively. Both Ts and Tm of cortical collagen from intact female rats decreased in parallel with age as previously found in male rats indicating that Ts and Tm measurements are interchangeable techniques in characterizing the thermal stability of bone collagen. Tm of trabecular collagen from intact rats decreased with age, however, with a decay only one-third of that for cortical collagen. The different rates possibly reflect different ages of collagen due to remodeling activity present in trabecular and minimal in cortical bone. Compared with control rats the Tm of trabecular collagen from gonadectomized and multiparous rats with a reported increased trabecular turnover rate was elevated, whereas only minor variations in Tm of cortical collagen were found. In conclusion, the thermal stability of bone collagen decreases with the age of the collagen. Increased bone turnover implies elevated thermal stability of bone collagen. Thus, thermal stability of bone collagen appears to be an indicator of bone turnover.

Aging↗

[Experimental study on the effect of Chinese traditional medicine "bone growth fluid" in the change of trace elements in bone lengthening area].

In order to study the effect of Chinese traditional medicine, "Bone Growth Fluid", on bone formation in bone lengthening, the limb lengthening model was made on goat to observe bone formation in the distracted area, and the content of the trace elements was determined. The bone-lengthening operation was carried out on the upper metaphysis of left tibia. The animals were divided into two groups following operation. From 2nd day afteroperation, "Bone Growth Fluid", 10 ml per kilogram body weight, was given daily to goats in the experimental group, and same amount of normal saline was given to goats in another group as control. The results showed-that new bone formation and bone remodeling in the experimental group appeared earlier than that in the control group, and the content of the trace elements was also improved. So Chinese Traditional medicine, "Bone Growth Fluid", could accelerate the accumulation of the trace elements in callus on the distracted sites and it might play some role in the promotion of osteogenesis and bone remodeling in bone lengthening.

Animals↗

Demineralized intramembranous bone matrix augments the healing of endochondral bone graft.

The aim of this study was to examine the osteogenic potential of demineralized bone matrix prepared from intramembranous bone (DBMIM) and to examine its effects on the healing of endochondral autogenous bone grafts. Twenty-four defects in 24 New Zealand white rabbits were used as experimental groups. Twelve defects were grafted with endochondral bone, and the other 12 defects were grafted with endochondral bone with DBMIM (EC-DBMIM). One rabbit from each group was sacrificed on days 1, 2, 3, 4, 5, 6, and 7 postgrafting, and the remaining 5 rabbits from each group were sacrificed on day 14 postgrafting. Another 8 defects in 4 rabbits were used as control groups: 4 defects were left empty (passive control), and 4 defects were grafted with rabbit skin collagen (positive control). They were all sacrificed at 14 days after grafting. Serial sections were made across the whole defect. Quantitative analysis was performed on 100 sections of the 14-day experimental groups by image analysis. Four hundred fourteen percent more new bone was formed in defects grafted with composite EC-DBMIM than in those grafted with endochondral bone alone (P < 0.0001). No bone was formed in either passive or positive controls. Histologic examination of the bone grafts revealed intermediate-stage cartilage, and immunohistochemical examination revealed earlier vascularization in the composite EC-DBMIM groups. In conclusion, DBMIM has extremely high osteoinductive properties and greatly enhances the integration of endochondral bone with defects of intramembranous bone in origin.

Analysis of Variance↗

Effect of cytokines on in vitro bone resorption by cells isolated from giant cell tumor of bone.

OBJECTIVE: To investigate the effect of cytokines on in vitro bone resorption by cells isolated from giant cell tumor of bone. METHODS: Mononuclear stromal cells and multinucleated giant cells (MGC) were isolated from 11 cases of giant cell tumor of bone (GCT) and their bone resorption capability in an in vitro cell-bone resorption model were tested. Expressions of some cytokines were detected by immunohistochemistry, Western blotting analysis and Enzyme-linked immunoabsorbent assay (ELISA) in the GCT. RESULTS: The results showed that MGCs of GCT had capability to resorb bone matrix directly. Fibroblast-like stromal cells (FC) could not only resorb bone matrix directly, but also secret unknown factors to facilitate bone resorption of MGC. Exogenous TNF-alpha could significantly increase the bone resorption by both kinds of stromal cells, while exogenous IL-1 did not. Expression rate of M-CSF and level of TNF-alpha in GCT were higher than in osteosarcoma and normal serum. CONCLUSIONS: The characteristic bone resorption behavior of GCT might be caused by its three major cell components. The M-CSF and TNF-alpha could promote their bone resorption capability.

Animals↗

Rabbit bone marrow response to bovine osteoinductive proteins and anorganic bovine bone.

The effects caused by the implantation of bioabsorbable hydroxyapatite (HA) bound to a pool of bone morphogenetic proteins (BMPs) and other bone noncollagenous hydrophobic proteins mixed with anorganic bovine bone inside rabbit bone marrow were assessed. Within the interior of hollow cylindric titanium prototypes, the following biomaterials were inserted: (1) test group: HA containing a pool of BMPs and noncollagenous hydrophobic proteins mixed with anorganic bovine bone; (2) control group: HA without any protein mixed with anorganic bovine bone; and (3) negative control group: blood clot. The cylinders were placed surgically into the medial portion of the tibiae of 7 rabbits in a manner that allowed the biomaterials to contact just the bone marrow. Morphometric analysis showed that: (1) the biomaterials containing the protein mixture resulted in significantly less new bone than the biomaterials without such a mixture; (2) the group without the protein pool formed larger amounts of bone within the cylinder when compared to the negative control (blood clot only); and (3) the biomaterials containing the protein pool did not show any difference in relation to the negative control. It was concluded that a pool of BMPs and other bone noncollagenous hydrophobic proteins had an inhibitory effect on osteogenesis, and that the biomaterials without a protein pool formed a favorable substrate to bone formation.

Animals↗

Preservation of bone morphogenetic protein in heat-treated bone.

In operations of bone tumors, reimplantation of resected bone after boiling or autoclaving is a simple means of obtaining both tumor necrosis and skeletal reconstruction. However, such reimplants lose their osteogenesity. We investigated whether bone inductive ability could be maintained in heat-treated bone. Bone morphogenetic protein (BMP) extracted from rabbit bone after heating for various periods at different temperatures was implanted into the muscles of mice to evaluate osteogenetic activity. The maximum new bone formation was observed in specimens treated at 70 degrees C for 10 minutes, followed by those treated at 70 degrees C for 15 minutes. We then measured the temperature in the center of a cortical bone heated in 0.15 N NaCl solution at 50 degrees, 60 degrees, 70 degrees, 80 degrees, and 90 degrees C. Cortical bone center temperature reached that of the surrounding solution within 2.5 minutes. These results indicated that heating at 70 degrees for 10 to 15 minutes was suitable for heat treated-bone to maintain bone inductive ability.

Animals↗

[Using platelet-rich plasma (PRP) to improve bone regeneration in implant bone defect].

OBJECTIVE: To evaluate the result of bone regeneration due to using PRP in combination with beta-TCP in bone defect adjacent to oral implantation. METHODS: Ten patients (6 males, 4 females, with an average age of 49.6 years) participated in this study. Seven of them underwent maxillary sinus augmentations, and 3 underwent GBR for peri-implant bone defects. PRP + beta-TCP was used in 4 cases and beta-TCP in other 6 as control. X-ray examinations were carried out prior to operation and in 1 week, at 3 months, 6 months after operation. After 4 - 6 months, 3 biopsy specimens were obtained at the time of the second stage operation in each group. RESULTS: Bone grafts healed well without any infection in all cases. Radiographs showed that bone grafts integrated together with the bone. The histological result showed that new bone was formed among particles of beta-TCP in both groups, but in PRP + beta-TCP group denser and better arranged woven bone was observed, and more new bone was formed into the micropores of the particles. CONCLUSIONS: The result in this study implied that PRP in combination with beta-TCP can improve bone regeneration in bone defect adjacent to oral implantation.

Adolescent↗

[Metabolic bone disease and bone quality].

On the progress of study concerned with pathology of metabolic bone disease such as osteoporosis, it has been known that most of bone strength can be explained by bone volume. As bone volume can be determine by bone mineral density (BMD) with dual-energy X-ray absorptiometry (DXA), it has been widely used for diagnosis of osteoporosis or efficacy of treatment. However, with the advance of bone morphometry, decrease of bone strength or existence of insufficiency fracture is influenced by not only loss of BMD but also deterioration of bone quality especially bone microstructure. In this chapter, we will give an outline of change of bone quality in metabolic bone disease.

Bone Diseases, Metabolic↗

[Bone structure and bone quality].

Bone strength is determined by bone mineral density, geometry of bone, microarchitecture of bone and quality of bone material. Recent data have shown that the prediction of bone strength can be greatly improved by including parameters of bone structure in the analysis. However, the relative importance of bone density and architecture in the etiology of bone fractures, an issue referred to as bone quality, is poorly understood. The challenge for the future will be to evaluate bone quality in vivo with the same or better accuracy than the invasive methods in use today.

Animals↗

The effects of demineralized bone matrix proteins and osteogenic protein-1 on bone cells isolated in culture.

With the growing number of bone-related traumas and the limitations of traditional bone repair, alternative methods of bone management must be investigated. Demineralized bone matrix protein (DBX) has been used to reconstruct bone. DBX, a type of demineralized bone matrix, is a combination of several different proteins including osteogenic protein-1 (OP-1). Osteogenic protein-1 or Bone Morphogenic Protein-7 (BMP-7) was the first BMP approved for clinical use in the United States. Previous studies have shown that proliferation of osteoblasts (bone forming cells) was stimulated by OP-1. However, the effects of DBM and OP-1 at the cellular level have not been clearly defined. MG-63 osteosarcoma cells were utilized as a model and subsequently plated onto 24 well tissue culture plates at a density of 1x 10(5) ml/well. Cells were exposed to different concentrations of DBX demineralized bone matrix and OP-1 for periods of 24, 48, and 72 hours and compared with untreated controls. After each incubation period, cell morphology, cell damage, cell number, and protein concentrations were determined. Results indicate a significant increase in cell number at 72 hours in cells treated with 30% (5.66 x 10(5)) and 100% (6.3 x 10(5)) DBX treated groups when compared with the control (1.4 x 10(5)). OP-1 results do not indicate a significant increase in cell number at the 24 and 48 hour treatment phases when compared with the control (p > 0.05), however, results do show a statistically significant difference (approximately twofold, p < 0.05) between the control cells (1.9 x 10(4)) and those cells treated with low (3.9 x 10(4)) and high (4.1 x 10(4)) concentrations of OP-1 at the 72 hour time phase. The increases in cell number indicate that both DBX and OP-1 are effective in stimulating cell growth. When comparing the results of the DBX treatments with those of the OP-1 treatments, the cells treated with DBX showed a more substantial increase in bone cell proliferation after treatment than those cells treated with OP-1. This does suggest that DBX provides the most effective treatment for bone cell proliferation. Closer evaluation of the morphology especially the changes occurring at the nuclear level need to be addressed in future studies.

Bone Demineralization Technique↗

[Bone metastases in breast cancer and its risk factor--follow up study by bone scintigraphy].

Breast cancer is considered to often involve bone metastasis. Early detection and treatment of bone metastasis are essential in improving the prognosis of this disease. In 47 patients with bone metastasis confirmed with bone scintigraphy, we examined the appearance time of bone metastasis; bone metastasis was frequently observed with the progress of stage, but no association with the appearance time was found. Age was not associated with the incidence of bone metastasis but was found to be closely related to its appearance time. That is to say, patients with breast cancer below 40 years of age showed relatively early bone metastasis. Bone scintigraphy is required every 6 months at least for 3 years after the operation. In patients over 40 years of age, on the other hand, bone scintigraphy is required only once a year but has to be continued for 5 years or more, because they often show relatively late bone metastasis.

Adult↗

[Bone infarction and fat island appearing as local defects in radionuclide bone marrow imaging].

Parallel studies of radionuclide bone marrow imaging and bone scanning are helpful in the early diagnosis of skeletal metastasis. In bone marrow imaging, most lesions are observed as a local defect. We had two cases of nonmetastatic lesions which appeared as local defects in bone marrow imaging. The first case was a male Hodgkin's disease patient, aged 48, who had been treated with frequent chemotherapy, including the administration of a large quantities of steroids. He complained of slight pain in the left shoulder. Without increased uptake in bone scanning, abnormal accumulation of 67Ga-citrate and a local defect in bone marrow imaging appeared, corresponding to localization of the pain. Suspecting bone marrow metastasis, we performed magnetic resonance imaging (MRI). An area of slightly decreased intensity in T1-weighted spin-echo images and lower intensity than fat tissue in T2-weighted images were observed, although it was slightly enhanced by Gd-DTPA. This lesion was diagnosed by biopsy as a bone infarction. The second case was that of a 69-year-old male lung cancer patient. Though no abnormality was revealed by bone scanning or 67Ga-citrate scintigraphy, an apparent defect at the 10th thoracic vertebra was observed in bone marrow imaging. It was not accompanied by pain. MRI was also performed in this case. This was depicted as a clearly defined high intensity area. This was diagnosed as a fat island, and no change has been seen in the seven months of follow up. In conclusion, it is necessary to consider the possibility of nonmetastatic lesions, when local defects appear in bone marrow imaging performed on cancer patients.

Adipose Tissue↗