One hundred and seven patients with malignant Hodgkin and non-Hodgkin lymphoma were examined by bone marrow scintigraphy, MRI of bone marrow and bone marrow biopsy to detect bone marrow infiltration. The findings of bone marrow imaging and biopsy were classified as normal (grade 0), suggesting reactive changes of bone marrow (grade 1) or suspicious for infiltration (grade 2). About half of all results of biopsy and imaging methods agreed completely. There was a difference of two steps in the classification in only 2 cases (MRI) and 5 cases (scintigraphy). In patients with chronic lymphocytic leukemia false negative findings by both bone marrow imaging techniques were frequent. Although a positive biopsy result must be accepted as proof of bone marrow infiltration, our results indicate that a negative biopsy does not exclude tumor involvement. In all 4 patients with infiltration suspected on MRI or scintigraphy results but with normal findings or reactive changes in the first blind biopsy, blind rebiopsy or guided rebiopsy confirmed the results of the imaging methods. In both patients evaluated at autopsy the preceding MRI and scintigraphy results were confirmed completely, although in both of these patients antemortem biopsy had indicated different findings. Based upon these observations, bone marrow scintigraphy and MRI should be routinely included in the staging of malignant lymphoma as an adjunct to blind bone marrow biopsy in the complete evaluation of bone marrow status. (orig./MG).

Osteoarthritis is generally considered a degenerative disorder driven by mechanical alteration of joint cartilage, with the bone changes being reactive to cartilage changes. According to this pathogenetic mechanism the only strategy to prevent osteoarthritis should be based on the so-called "chondro-protective agents". However, a number of recent finding suggests that both the initiation and the progression of the disease is driven by subchondral bone changes reactive to mechanical microdamages. These increase osteoblastic activity at the "tide-mark" with consequent enlargement of the epiphyses and osteophyte formation. The increased bone turnover is secondary to overproduction of cytokines that diffuse to cartilage tissue, where they suppress condrocyte activity and activate metallo-proteases. Preliminary observational finding and experimental data showed that inhibitors of bone turnover might slow osteoarthritis progression. The pathogenetic hypothesis for osteoarthritis illustrated here provides the rational for a new therapeutic approach to the disease. PMID:12461574

Bone scans of patients with diabetic osteoarthropathy of the ankle and foot were characterized by a combination of diffuse and focal increased uptake, similar to that seen with hyperemia and reactive new bone formation. Scintigraphy showed more extensive abnormalities than radiography, with the scan abnormalities sometimes preceding the radiographic changes. The clinical and scintigraphic appearance of osteoarthropathy may improve following strict diabetic control and non-weight-bearing.

The X-ray images observed in 4 patients with bone hemangiomatosis and in 1 patient with lymphamgiomatosis were discussed from the viewpoint of localization, morphologic pattern and evolution. Proceeding from their own observations and available data in the literature, the authors assume that most important for the diagnosis of hemangiomatosis are: intact bone structure outside the angiomatosis lesions; predominantly excentric and superficial localization in the long bones, with or without demineralization of the cordial layer; Extraosseal development; secondary changes in the adjacent soft tissues, due to hematomas or accompanying angiomatosis; more pronounced reactive changes in more adult patients in the affected foci and zones; absence of periostal reaction. The great variability requires examination of several skeletal segments: skull, ribs, pelvis long tubular bones.

AbstractObjective To assess temporal changes in cartilage and bone morphology, reactive oxygen species (ROS), and vascularization in rats with monosodium iodoacetate (MIA)-induced osteoarthritis (OA), using advanced imaging methodologies. Methods Right knees of 8-week-old male Wistar rats were injected with 1 mg MIA in 50 l saline and left knees were injected with 50 l saline as controls. After 1, 2, and 3 weeks (n = 5 at each time point), changes in cartilage morphology and composition were quantified using equilibrium partitioning of an ionic contrast agent microfocal computed tomography (CT), and changes in subchondral and trabecular bone were assessed by standard CT. ROS were characterized by in vivo fluorescence imaging at 1, 11, and 21 days (n = 5 at each time point). Three weeks fol...

Objectives Evaluate relationships between MRI and clinical/laboratory/radiographic findings in rheumatoid arthritis (RA). Methods 637 methotrexate-naive patients (GO-BEFORE) and 444 patients with active RA despite methotrexate (GO-FORWARD) were randomly assigned to subcutaneous placebo + methotrexate, golimumab 100mg + placebo, golimumab 50mg + methotrexate, or golimumab 100mg + methotrexate every-4-weeks. In GO-BEFORE(n=318) and GO-FORWARD(n=240) substudies, MRI of dominant wrist/metacarpophalangeal joints were scored for synovitis, bone oedema and bone erosion (RA MRI scoring (RAMRIS) system). Relationships between RAMRIS scores and serum C-reactive protein (CRP), 28-joint count disease activity score (DAS28–CRP) and van der Heijde modified Sharp (vdH-S) scores were assessed. Results Baseline and weeks 24/28 DAS28–CRP, CRP, and vdH-S generally correlated well with baseline and week 24 RAMRIS synovitis, oedema and erosion scores. Early (week 4) CRP changes correlated with later (week 12) RAMRIS synovitis/oedema change scores; earlier (week 12) changes in some RAMRIS scores correlated with later (weeks 24/28) changes in vdH-S. Significant correlations between RAMRIS change scores and clinical/radiographic change scores were weak. Conclusions MRI and clinical/laboratory/radiographic measures generally correlated well. Associations between earlier changes in CRP and later changes in RAMRIS synovitis/osteitis were observed. Changes in MRI and clinical/radiographic measures did not correlate well, probably because MRI is more sensitive than radiographs and more objective than DAS28–CRP. PMID:21749708

We assessed the value of contrast-enhanced fat-suppressed MRI on nine patients with osteoid osteomas and osteoblastomas. The results were compared with plain films, bone scintigraphy, computed tomography (CT) and pathological specimens. On contrast-enhanced fat-suppressed T1-weighted images the non-calcified nidi showed homogeneous enhancement, whereas the calcified lesions showed a ring enhancement sign that was proportional in intensity to the extent of the remaining part of the vascularized nidus. The degree of bone marrow and soft tissue enhancement was relative to the size and reactive inflammatory changes of the lesions. Although CT was diagnostic in most of the cases and more specific to show the calcified lesions, MRI was confirmatory in one case. We concluded that, although CT is the primary diagnostic investigation in osteoid osteomas, MRI can be reserved for equivocal cases. (orig.)

Magnetic resonance imaging (MRI) is not only an excellent imaging modality for the demonstration of morphological changes but is also capable of providing pathophysiological and pathoanatomic information about various spinal diseases. Different techniques offer opportunities to demonstrate the degree of water content, the vascularity of tissue components, the accumulation of fat, and new bone production. Thus MRI closely reflects the initial phase as well as the progression of pathoanatomic changes during the evolution of a disease. Due to the high sensitivity of MRI, abnormalities are often established at an early stage of discovertebral disease, when etiological diagnosis may be difficult. The specificity of MRI findings lags behind its sensitivity; similar changes can be demonstrated in etiologically different disease entities, which reflects the limited reactive possibilities of the osteoarticular system. In fact, the MRI morphological and signal intensity features of different discovertebral lesions are commonly determined more by their location and by the reactive capabilities of disc and bone than by their etiology. Early and exact MRI differentiation of various discovertebral lesions is of the utmost clinical importance for prompt institution of appropriate therapy. (orig.)

Ethanol has been known to induce osteopenia. However, the cellular and molecular mechanisms responsible for its effect have not been well characterized. This study investigated the effects of ethanol on bone metabolism and osteoclastogenesis using rats fed an ethanol-containing liquid diet (35% of calories from ethanol) for 3 weeks. Ethanol increased the activities of bone tartrate-resistant acid phosphatase (TRAP) and cathepsin K, without affecting the levels of serum osteocalcin or bone alkaline phosphatase activity. Histological analysis showed an increased number of osteoclasts in the proximal tibia, but no significant change in the number of osteoblasts. The mRNA levels of receptor for activation of NF-?B (RANK), c-fos, c-jun, TRAP and cathepsin K were significantly increased, although those of macrophage colony-stimulating factor and c-fms were unaltered. The mRNA and protein levels of PU.1 and microphthalmia-associated trascription factor (MITF) also increased. Further, the osteoclastic differentiation of bone marrow-derived macrophage/monocyte precursor cells (BMMs) in vitro was stimulated by ethanol. The increased osteoclastogenesis of BMMs was associated with increased levels of RANK, PU.1 and MITF expression, activated extracellular signal-regulated kinase (ERK), and reactive oxygen species (ROS). Higher lipid peroxide levels and lower glutathione levels were also observed in the serum of the ethanol-fed rats. These results suggested that ethanol promoted osteoclastogenesis by increasing RANK expression through increases in the production of ROS, activation of ERK and expression of PU.1 and MITF. PMID:22576626

We have used a pharmacological approach to study the mechanisms underlying the rat lung injury and the airway reactivity changes induced by inhalation of formaldehyde (FA) (1% formalin solution, 90 min once a day, 4 days). The reactivity of isolated tracheae and intrapulmonary bronchi were assessed in dose-response curves to methacholine (MCh). Local and systemic inflammatory phenomena were evaluated in terms of leukocyte countings in bronchoalveolar lavage (BAL) fluid, blood, bone marrow lavage and spleen. Whereas the tracheal reactivity to MCh did not change, a significant bronchial hyporesponsiveness (BHR) was found after FA inhalation as compared with naive rats. Also, FA exposure significantly increased the total cell numbers in BAL, in peripheral blood and in the spleen, but did not modify the counts in bone marrow. Capsaicin hindered the increase of leukocyte number recovered in BAL fluid after FA exposure. Both compound 48/80 and indomethacin were able to prevent the lung neutrophil influx after FA, but indomethacin had no effect on that of mononuclear cells. Following FA inhalation, the treatment with sodium cromoglycate (SCG), but not with the nitric oxide (NO) synthase inhibitor L-NAME, significantly reduced the total cell number in BAL. Compound 48/80, L-NAME and SCG significantly prevented BHR to MCh after FA inhalation, whereas capsaicin was inactive in this regard. On the other hand, indomethacin exacerbated BHR. These data suggest that after FA inhalation, the resulting lung leukocyte influx and BHR may involve nitric oxide, airway sensory fibers and mast cell-derived mediators. The effect of NO seemed to be largely restricted to the bronchial tonus, whereas neuropeptides appeared to be linked to the inflammatory response, therefore indicating that the mechanisms responsible for the changes of airway responsiveness caused by FA may be separate from those underlying its inflammatory lung effects.

Ten patients who had had osteosynthetic repairs of bone defects carried out by means of bone grafts were studied. It was shown that magnification radiography permitted better and more complete evaluation of the healing process. Trabecular bone structure can be recognised and changes in the configuration and position of the trabeculae during their incorporation into the bone can be evaluated.

The sensitivity of Tc99m-MDP-bone-scintiscanning in the diagnosis of temporal bone fracture was found to that of conventional radiography if the patients were examined 10 days after the trauma. Temporal bone osteomyelitis with concomitant moderate osteosclerosis was demonstrated by bone scintigraphy in 5 cases of mastoiditis with atypical symptoms. A case of apicitis was for the first time demonstrated by scintigraphy. A low sensivity of /sup 67/Ga-scintigraphy was demonstrated by positive Tc99m-bone-scintigraphy and negative /sup 67/Ga-scintigraphy in a patient with atypical mastoiditis. Tc99m-scintigraphy was negative in 5 cases of otitis media suppurative and in 3 cases of otitis media chronica cum cholesteatoma, all with slight degree of osteosclerosis in the mastoid. The sensitivity of Tc99m-bone-scintigraphy in fracture and osteomyelitis of the temporal bone seems to be a function of the amount of reactive new bone formed.

Immunohistochemical studies were performed with monoclonal antibodies (MAbs) reactive on paraffin embedded bone marrow biopsies in 19 patients with myelodysplastic syndromes, 8 of them during r-gamma-interferon treatment. CD15 MAbs stained mature myeloid cells predominantly located close to the bone...

On the basis of the data of rheovasography (RVG) and laser Doppler flowmetry, comparative analysis of age-related changes in the peripheral blood circulation in hand tissues has been performed in 36 apparently healthy subjects aged 4?30 years and in 19 patients aged 18?50 years under the conditions of prolonged traction during surgical lengthening of finger bone stumps. The age-related changes in RVG are characterized by a higher volumetric blood content of tissues in children and adolescents, a decrease in the peripheral vascular tone, and wavelike recovery of capillary blood flow during reactive hyperemia, which is evidence for an unstable capillary tone. The dynamics of RVG indices during graded stretching in vivo (distraction) shows the dominance of an enhanced peripheral tone of arter...

The purpose of the present report is to update information and reference values for the human skeleton to represent Western Man for use in radiological protection. Data are provided for the fresh weight of the skeleton and individual bones; the weight of the ``dry`` or ``dry, fat-free`` skeleton and bones; the relative amounts, the surface-to-volume ratios, and the age and gender-related changes in characteristics of both compact and trabecular bone; bone remodelling; bone density; and composition of bones. Cartilage, bone marrows, skeletal blood flow and blood content, teeth are also covered. Finally a summary is given of the reference weights of major skeletal components. (UK).

When bone is rapidly induced by recombinant human bone morphogenetic protein-2 (rhBMP-2), more noncollagenous proteins (NCPs) are accommodated among the collagen meshwork. These NCPs are then removed, resulting in highly mineralized mature bone. However, few reports have focused on changes in the bone matrix of rhBMP-2-induced bone. In the present study, rhBMP-2 with an artificial carrier was implanted over bone defects in rat calvariae, and changes in the distribution of osteopontin (OPN), the degree of mineralization and speed of bone formation were investigated histochemically and radiographically. Dome-shaped areas of newly formed bone observed at postoperative week 2 were intensely immunoreactive for OPN and intensely labeled with calcein, but were not as radiopaque as the preexisting bone. At postoperative week 8, intense immunoreactivity was detected only on cement lines and in small discrete areas on the flattened domes. The matrix was as radiopaque as, and indistinguishable from, the preexisting bone. Only thin linear labeling of calcein was found on the bone surface. These findings suggest that, in rhBMP-2 induced bone, production of OPN is increased when the rate of bone formation is high, and that OPN produced in the early stage of bone formation is removed during bone remodeling to create a highly mineralized mature bone matrix.   

The aim of this study was to establish an objective method for quantitative evaluation of bone volume change after sinus augmentation. 11 sinuses in 9 patients were evaluated by computed tomography images taken before treatment (T0), and 3 months (T1) and at least 1 year (T2) after sinus augmentation. Based on the 3D digital subtraction technique, augmented bone images were extracted and bone volumes were calculated from voxel numbers of the extracted images. The mean augmented bone volumes at T1 and T2 were 2.46cm^3 and 1.85cm^3, respectively. These bone volume changes were statistically significant and the mean bone volume change+/-SE was -24.8%+/-6.1%. Loss of augmented bone was observed in all except one of the patients. The correlation coefficient between bone volume change and elapse...

Acromegalic arthropathy is one of the most frequent manifestations occurring in acromegaly patients. In contrast, rheumatoid arthritis (RA) is a rare clinical complication in acromegaly patients. Here, we report a 70-year-old Japanese woman with acromegaly, who complained of bilateral finger stiffness and polyarthralgia two months after transsphenoidal surgery of a growth hormone (GH)-secreting pituitary adenoma. Postoperative levels of serum GH and insulin-like growth factor-1 (IGF-1) were markedly decreased without any secretory deficiency of other anterior pituitary hormones. Hand X-ray did not show typical RA changes; however, erosive changes in carpal bones were clearly detected by magnetic resonance imaging with gadolinium enhancement. Based on the levels of serological markers in the patient following surgery including C-reactive protein, rheumatoid factor and matrix metalloproteinase-3, anti-rheumatic therapy was subsequently commenced. Regardless of the levels of GH and IGF-1, acromegaly patients frequently complain about joint-related symptoms even after remission. Therefore, careful observation of bone erosive changes and immunological activity in acromegaly patients is required when joint-related symptoms persist.   

The pathologic specimens of 18 osteosarcomas of long bones were examined to correlate histologic abnormalities with abnormalities seen on preoperative /sup 99m/Tc pyrophosphate or methylene diphosphonate bone scans. Seven scans accurately represented the extent of the tumor. Eleven scans disclosed increased activity extending beyond the radiographic abnormalities. In eight of these, there was no occult tumor extension and in the other three, the scan activity did not accurately portray the skip metastases that were present. Therefore, these 11 scans demonstrated the falsely extended pattern of uptake beyond the true limits of the tumors. Pathologic slides were available for 10 of the 11 areas of bone that exhibited extended uptake. In two instances, there was no pathologic abnormality. In the other eight cases we found marrow hyperemia, medullary reactive bone, or periosteal new bone. This is the first description of these histologic abnormalities of medullary bone in areas of extended uptake on radionuclide bone scans.

We have selected heat-treated bone allografts as the graft material since the Tokai Bone Bank, the first regional bone bank in Japan, was established in 1992. In this study, we examined changes in bone mineral density (BMD), and morphology observed by magnetic resonance imaging (MRI), and histological findings of bone grafts in cases followed up for 7?10 years after bone grafting to grasp the remodeling of heat-treated cortical bone allografts for posterior lumber interbody fusion (PLIF). BMD of bone grafts was reduced by half at 10 years after grafting. MRI revealed that bone grafts were indistinguishable initially in only 22.2% of cases, whereas after a lengthy period of 10 years distinguishable in many cases. Histologically, new bone formation at the graft-host interface was observed ea...

Context: Age-related bone loss is associated with progressive changes in bone remodeling characterized by decreased bone formation relative to bone resorption. Both trabecular and periosteal bone formation decline with age in both sexes, which contributes to bone fragility and increased risk of fractures. Studies in rodents and humans revealed that, independent of sex hormone deficiency, the age-related decline in bone formation is characterized by decreased osteoblast number and lifespan and reduced bone-forming capacity of individual osteoblasts. An important clinical question is to identify the mechanisms involved in the age-related defective bone formation. Evidence Acquisition: The mechanisms discussed in this review are based on a PubMed search and knowledge of the authors in the field. Evidence Synthesis: Available basic and clinical studies indicate that multiple mechanisms are involved in the alterations of osteoblastogenesis and the resulting decline in bone formation with aging. Notably, the age-related osteoblast dysfunctions and defective bone formation are caused by a number of extrinsic clinical factors that inhibit anabolic signaling pathways in bone. Thus, targeting these pathways can abolish age-related bone loss. Conclusions: The identification of extrinsic mechanisms involved in osteoblast dysfunctions associated with aging improves our knowledge of age-related bone loss and provides a basis for therapeutic intervention to improve bone formation and bone mass in the aging population.

We evaluated the effects of intermittent slow-release sodium fluoride (SRNaF) and continuous calcium citrate therapy on cortical bone histology, reflection ultrasound velocity (material strength) and back-scattered electron image analysis (BEI) in 26 osteoporotic patients before and following therapy. All measurements were made on transiliac crest bone biopsies obtained before and following 2 years of therapy in each patient. For all 26 patients there were no significant changes in cortical bone histomorphometric parameters. In 15 patients in whom bone material quality was assessed by reflection ultrasound, there was no change in velocity (4000 +/- 227 SD to 4013 +/- 240 m/s). BEI disclosed no mineralization defects or the presence of woven bone. Mean atomic number (density) of bone increased slightly, but significantly (9.261 +/- 0.311 to 9.457 +/- 0.223, P = 0.031). While these changes are less marked than those observed for cancellous bone, they indicate that this form of therapy does not adversely affect cortical bone remodelling.

Reasons for performing the study: Lateral condylar (LC) fractures of the third metacarpus (McIII) are a common reason for euthanasia in racehorses, and may be the result of repetitive overloading or cumulative pathological change. Magnetic resonance imaging (MRI) allows monitoring of bone and cartilage to detect pathological and adaptive changes that may be precursors of fracture. Objectives: To describe bone and cartilage MRI features in the distal condyles of McIII of Thoroughbred racehorses, with and without condylar fracture. Hypotheses: 1) A greater degree of bone and cartilage adaptation or pathology will be seen in fractured McIIIs compared with their respective contralateral McIIIs. 2) Contralateral McIIIs will have a greater degree of bone and cartilage adaptation or pathology than McIIIs from control horses that did not sustain a LC fracture. Methods: The McIIIs from 96 horses subjected to euthanasia at racecourses were divided into 3 groups: Group 1: nonfractured bones from horses without LC fracture; Group 2: nonfractured bones from horses with unilateral LC fracture; and Group 3: fractured bones from horses with unilateral LC fracture. The MR images were examined and graded for bone and cartilage changes. Results: Nine percent of Group 1 (n = 9) and 11% of Group 2 bones (n = 5) had incomplete LC fractures. Focal palmar necrosis was most frequently detected in bones from Group 1 (12%) compared with Groups 2 (9%) and 3 (4%). The prevalence of bone and/or cartilage abnormalities tended to increase from Group 1 to Group 2 to Group 3. Conclusions: Magnetic resonance imaging is able to detect cartilage and bone changes that may be associated with LC fracture. There was no significant difference in bone/cartilage changes between bones from Groups 1 and 2, despite increased pathology in Group 2 bones. Potential relevance: Periodic monitoring of bone and/or cartilage changes in distal McIII of Thoroughbred racehorses may help to prevent catastrophic LC fractures. PMID:22256885

Paget's disease of bone is characterized histologically by abnormal architecture of bone matrix. Extensive areas of woven bone and numerous scalloped cement lines occur as a result of increased irregular remodeling. Noncollagenous proteins (NCP) play an important role in the organization and mineralization of bone matrix and promote distinct cell-matrix interactions necessary for normal remodeling. To gain insight into the pathological changes in the biochemical composition of Pagetic bone, the distribution of NCPs in the calcified matrix of bone from patients with known Paget's disease was compared to that of bone from normal healthy volunteers. Undecalcified plastic-embedded sections of bone were stained immunohistochemically using antibodies generated against several NCPs. In Pagetic and normal bone a similar distribution of osteopontin was observed at cement (reversal) lines, whereas significant differences were observed in the distribution of osteopontin in the matrix immediately adjacent to Haversian canals, where initial osteoclast recruitment and attachment occur. The differences in osteopontin distribution appeared to be related to the state and severity of the disease. Site-specific differences in the distribution of osteonectin, osteocalcin, and decorin were also observed between normal bone and cortical and periosteal de novo Pagetic bone, whereas the distribution of other matrix proteins, such as biglycan, was unchanged. We conclude that these site-specific changes in the biochemical distribution of NCPs in Pagetic bone probably reflect abnormal production and/or incorporation during bone remodeling and may lead to disorganized matrix assembly and mineralization as well as have profound effects on bone cell functions. PMID:8626840

Bone quality is an evaluation index often applied in order to interpret clinical observations made upon bone health, such as bone mineral density, micro and macro architecture, and mineral content. Conventional inspection techniques do not provide full information on trabecular bone quality. This study shows the high resolution potential and the non-destructive character of X-ray microtomography and microfluorescence upon the application of such techniques for evaluating bone quality. The mineral content assessment was performed by two-dimensional concentration mappings of calcium, zinc, and strontium. The results showed significant changes in bone morphology. PMID:22206910

Bone quality is an evaluation index often applied in order to interpret clinical observations made upon bone health, such as bone mineral density, micro and macro architecture, and mineral content. Conventional inspection techniques do not provide full information on trabecular bone quality. This study shows the high resolution potential and the non-destructive character of X-ray microtomography and microfluorescence upon the application of such techniques for evaluating bone quality. The mineral content assessment was performed by two-dimensional concentration mappings of calcium, zinc, and strontium. The results showed significant changes in bone morphology.

Background: Infections can influence bone metabolism of neonates, which may lead to changes in some bone metabolism biomarkers. The purpose of this study was to determine whether serum bone alkaline phosphatase (BALP), osteocalcin (OC) and beta carboxy-terminal peptide of type I collagen (CTX), as s...

Angiotensin II (Ang II) contributes to the pathogenesis of hypertension and other cardiovascular diseases. Ang II induces a pro-oxidative, proinflammatory, and prothrombogenic phenotype in vascular endothelial cells. Although the peptide promotes the recruitment of leukocytes and platelets and induces oxidative stress in the microvasculature, it remains unclear whether and how the blood cell recruitment is linked to the production of reactive oxygen species. In this study, we addressed the contributions of Ang II type 1 receptors (AT(1)r) and gp91(phox) to the recruitment of leukocytes and platelets and reactive oxygen species production in venules during chronic (2-week) infusion of Ang II in wild-type (WT) and mutant mice. Intravital video microscopy was used to measure the adhesion and emigration of leukocytes, the adhesion of fluorescently labeled platelets, and dihydrorhodamine oxidation (a measure of oxidative stress) in cremaster muscle postcapillary venules. In WT mice, Ang II infusion induced a time-dependent increase in the adhesion of leukocytes and platelets and enhanced reactive oxygen species production in venules. These changes in blood cell adhesion and reactive oxygen species production were not observed in AT(1)r(-/-) mice, AT(1)r(-/-) bone marrow chimeras (blood cells deficient in AT(1)r), gp91(phox-/-) mice, gp91(phox-/-) chimeras (blood cells or endothelial cells deficient in gp91(phox)), and in WT mice rendered granulocytopenic via intraperitoneal injection of antimouse granulocyte receptor 1 antibody. Thrombocytopenic WT mice (platelets depleted by intraperitoneal injection of rabbit antimouse thrombocyte antiserum) responded similar to WT mice. These findings implicate leukocyte-associated AT(1)r and gp91(phox) in the induction of the pro-oxidative, proinflammatory, and prothrombogenic phenotype assumed by microvessels that is chronically exposed to elevated Ang II. PMID:23090770

CONTENTS. Section. S%fMIXRY ..................................... INTRODUCTION . ... 17 is. APOLLO 16 LEFT OS CALCIS MINERAL CONTENT CHANGE .... 17. 4POLLO 16 ...... Bone Disease, Excerpta Medica Foundation (Amsterdam), 1972, pp.

In order to model the vascularization stage of periodontal recovery, platelet-rich plasma (PRP) was applied to the sockets of the beagle dog's dentition. Microvascular resin injection was performed 14, 30, and 90 days later and examined by light and scanning electron microscopy to investigate the relationship between bone formation and vascular changes. Bone formation ratios were measured from the scanning electron microscopic images. Fourteen days after the operation, newly formed blood vessels filled the untreated sockets, except for the center portion. These blood vessels had regenerated along the pre-existing bone wall of the socket. In the sockets treated with PRP, however, the sockets were filled with newly formed bone, and regenerated blood vessels were surrounded by new bone. Thirty days after the operation, the insides of the sockets were filled with newly formed porous bone in both groups. In untreated sockets, porous new bone formation was observed along the blood vessels, but in sockets treated with PRP, bone trabecula and blood vessels were arranged in the porous bone. Ninety days after the operation, both treated and untreated sockets contained regenerated normal bone tissue, with bone marrow reproduced along the trabeculae and vascular networks observed. However, the bone formation ratios of the PRP-treated sockets were significantly higher than the untreated sockets after 14 and 30 days. At 90 days, nearly identical bone formation was measured in both groups. Taken together, these observations suggest that PRP application to the extraction sockets advanced bone regeneration and promoted regeneration of the blood vessels.   

Patients with anorexia nervosa (AN) usually have abnormal bone and bone marrow metabolism resulting in osteopenia and serous bone marrow change. There is an increased risk of stress/insufficiency fractures and these can be the first presentation of AN. This case report describes a patient with previously undiagnosed AN who presented with foot pain. The serous bone marrow changes of AN were found to mask the MR imaging features of stress fractures, as both had low T1w and high T2w and STIR signal intensities. Contrast enhancement was not helpful but actually masked fractures. Scintigraphy was helpful. The radiologist might be the first clinician to raise the possibility of AN and should be aware of the difficulties in diagnosing stress fractures in bones with underlying serous bone marrow change. In this severe case of AN even the heel fat pad and the fat pad in Kager's triangle had undergone serous change.

Abstract Hematopoietic stem cells (HSC) are maintained in a tightly regulated bone microenvironment constituted by a rich milieu of cells. Bone cells such as osteoblasts are associated with niche maintenance as regulators of the endosteal microenvironment. Bone remodeling also plays a role in HSC mobilization although it is poorly defined. The effects of zoledronic acid (ZA), a potent bisphosphonate that inhibits bone resorption, were investigated on bone marrow cell populations focusing on HSCs, and the endosteal and vascular niches in bone. ZA treatment significantly increased bone volume and HSCs in both young and adult mice (4 week and 4 month old, respectively). ZA increased vessel numbers with no overall change in vascular volume in bones of young and had no effect on vasculature in ...

Numerous reports of successful radiocarbon dating of cremated bones have emerged during the last decade. The success of radiocarbon dating cremated bones depends on the temperature during burning and the degree of recrystallisation of the inorganic bone matrix. During cremation bones undergo major morphological and mineralogical changes which have raised some interesting questions and discussion on the origin of the carbon source in archaeologically cremated bones. Recent laboratory experiments reveal that the properties of the combustion atmosphere play a significant role regarding the source carbon in cremated bones. Thus radiocarbon dating cremated bones is potentially dating the wood used for the cremation fire. Here we compare a high precision radiocarbon dated human bone with an asso...

With the recent Fukushima incident, there is an urgent need to find cost effective and workable permeable reactive barrier (PRBs) for the remediation/retardation of problematic radionuclides. Catfish bones were calcined at various temperatures (400–1100°C) to remove the organic matter (87.1 mg·g?1) and to change the structural properties of the hydroxyapatite (HAP). Increasing temperatures increased the HAP crystallinity as indicated by a decrease in lattice strain (0.0098 to 0.00135) and an increase in crystallite sizes (5.0 × 10?8 to 7.7 × 10?8 m). There was also an observed decrease in specific surface areas (98.9 to 0.99 m2·g?1) and increase in particle sizes (50 to 1000 nm). The sorption densities of Sr2+ decreased with increasing calcination temperatures, from 0.34 to 0.05 mmol·g?1. However, once normalized for surface area, the sorption densities increased from 1.8 to 5.9 mmol·m?2. Overall, this research has important implications for the design of hydroxyapatite PRBs with higher calcination temperatures producing a more reactive material with larger particle sizes for increased permeability. Lower calcination temperatures produced amorphous HAP material, which released more aqueous PO43? and resulted in the precipitation of strontium phosphates, ultimately reducing the permeability of PRBs.   

Discoveries are rapidly being made in multiple laboratories that shed "light" on the fundamental molecular and cellular mechanisms underlying the use of low level light therapy (LLLT) in vitro, in animal models and in clinical practice. Increases in cellular levels of respiration, in cytochrome c oxidase activity, in ATP levels and in cyclic AMP have been found. Increased expression of reactive oxygen species and release of nitric oxide have also been shown. In order for these molecular changes to have a major effect on cell behavior, it is likely that various transcription factors will be activated, possibly via different signal transduction pathways. In this report we compare and contrast the effects of LLLT in vitro on murine embryonic fibroblasts, primary cortical neurons, cardiomyocytes and bone-marrow derived dendritic cells. We also examined two human cell lines, HeLa cancer cells and HaCaT keratinocytes. The effects of 810-nm near-infra-red light delivered at low and high fluences were addressed. Reactive oxygen species generation, transcription factor activation and ATP increases are reported. The data has led to the hypothesis that cells with a high level of mitochondrial activity (mitochondrial membrane potential) have a higher response to light than cells with low mitochondrial activity.

This work presents a computational model for bone remodelling around cementless stems. The problem is formulated as a material optimisation problem considering the bone and stem surfaces to be in contact. To emphasise the behaviour of the bone/stem interface, the computer model detects the existence of bone ingrowth during the remodelling; consequently, the contact conditions are changed for a better interface simulation. The trabecular bone is modelled as a strictly orthotropic material with equivalent properties computed by homogenisation. The distribution of bone relative density is obtained by the minimisation of a function that considers both the bone structural stiffness and the biological cost associated with metabolic maintenance of bone tissue. The situation of multiple load conditions is considered. The remodelling law, obtained from the necessary conditions for an optimum, is derived analytically from the optimisation problem and solved numerically using a suitable finite element mesh. The formulation is applied to an implanted femur. Results of bone density and ingrowth distribution are obtained for different coating conditions. Bone ingrowth does not occur over the entire coated surfaces. Indeed, we observed regions where separation or high relative displacement occurs that preclude bone ingrowth attachment. This prediction of the model is consistent with clinical observations of bone ingrowth. Thus, this model, which detect bone ingrowth and allow modification of the interface conditions, are useful for analysis of existing stems as well as design optimisation of coating extent and location on such stems. PMID:11784535

Objective To study the utility of CT for detection of small bone lesions in POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes) syndrome. For patients with a solitary bone lesion, irradiation is a first-line treatment, whereas systemic chemotherapy is indicated for patients with multiple bone lesions. Therefore it is important to correctly identify the number of bone lesions. Methods We studied the sensitivity of chest/abdomen/pelvic CT to detect bone lesions in 28 patients with POEMS syndrome. 99mTc-HMDP bone scintigraphy was performed in 14 patients, and the results were compared with CT. Results CT showed multiple bone lesions in 68% of the 28 patients, and 71% of the lesions had a diameter <10 mm. In 14 patients who underwent both CT and scintigraphy, bone lesions were detected in 57% by CT and in 79% by scintigraphy, but the location and nature of the identified lesions were considerably different; CT frequently showed small lesions (diameter <10 mm) in the vertebrae and pelvis, which were not detected by scintigraphy, whereas scintigraphy could show lesions in the skull and long bones. Overall, by using both examinations, multiple bone lesions were found for 86% of patients. Conclusion CT is particularly useful to detect small bone lesions. CT and bone scintigraphy are complementary, and therefore both should be performed for bone survey in POEMS syndrome.   

The objective of this study was to gain a better understanding of the relationship between age, activity level (as indicated by runners and non-runners), and site specific bone mass and long bone structural parameters related to long bone cross-sectional geometry. We hypothesized that bone mass measurements and long bone structural properties would be decreased with age but would be enhanced by a higher activity level. Currently, the most widely used and accepted method of noninvasive skeletal assessment is dual energy x-ray absorptiometry (DXA) which measures regional and whole body changes in bone mineral content (BMC) and areal bone mineral density (BMD). However, whole bone stiffness and strength are not solely dependent on bone mass, but also upon its cross-sectional shape and distribution. Bone densitometry has been previously used to obtain cross-sectional properties of bone in a single scan plane. In a new approach using three noncoplanar scans, this technique was extended to obtain the principal moments of inertia and orientations of the principal axes of each scan cross-section. This method has been validated using aluminum phantoms and cadaveric long bones. The method was used in this study to investigate structural properties in the long bones of the lower limb as a function of age and activity level in women.

The authors report 14 cases of Wegener granulomatosis in which one or more paranasal sinuses were obliterated by bone. The maxillary antra were involved in all cases, with the other sinuses being affected less frequently. These changes are thought to result from chronic bacterial sinusitis superimposed on the granulomatous vasculitic process. Computed tomography dramatically demonstrated the bone changes, consisting of a combination of sinus wall thickening and trabeculated new bone formation within the sinuses.

The purpose of this study was to clarify the effect of decreased food consumption on evaluation of myelotoxicity in routine general toxicity studies. Male rats were divided into the following 7 groups: 12, 15, and 18 mg/kg 5-fluorouracil (5-FU) treatment groups (FU12, FU15 and FU18); dietary restriction groups (R12, R15 and R18 receiving the same amount of food as the rats in the FU12, FU15 and FU18 groups, respectively); and a nontreated control group (NT). We compared the changes in body weight, hematology and the results of cytological analyses of bone marrow and histopathology among the groups after administration and recovery periods of 14 and 7 days, respectively. At the end of the administration period, the FU15 and FU18 groups showed decreases in many hematologic and bone marrow parameters that were all similar to those in the corresponding dietary restriction groups (R15 and R18). A granulocyte abnormality (polyploidy: frequency of 1% or less) was also observed in all 5-FU treated groups. At the end of the recovery period, increases in the reticulocyte and platelet counts and extramedullary hematopoiesis of the spleen were observed in the 5-FU treated groups. These results indicate that the results of general toxicity studies in rats should be evaluated in consideration of dietary restriction effects when food consumption is decreased at about 30-40% or more. Careful morphological observation of hemocytes would be helpful in distinguishing the effect of a drug from that of dietary restriction in relation to hematological and bone marrow parameters. Performance of a recovery test to determine the reactive response of hematopoiesis is also recommended.   

Medullary bone is formed reticularly in the bone marrow cavity of the long bones of female birds. Although this bone matrix contains fewer collagen fibers and more acid mucopolysaccharides than cortical bone, it is not clear that the expression pattern of osteoblast phenotypic genes during bone remodeling. Therefore, 17?-estradiol (E2)-treated male Japanese quails were used to examine the temporal expression patterns of osteoblast phenotypic genes, and to simultaneously confirm the morphological changes occurring in the bone marrow cavity during medullary bone formation and resorption. After E2 treatment, bone lining cells proliferated and developed into mature osteoblasts that had intense alkaline phosphatase (ALP) activity. These cells began to form medullary bone that contained acid mucopolysaccharides and tartrate-resistantacid phosphatase. Runt-related gene 2 (Runx2) mRNA was stably expressed throughout the process. The expression of both ALP and type I collagen mRNAs increased initially, and then rapidly decreased after day 7, while osteoclasts began to resorb medullary bone at day 5. The expression of bone matrix-related genes peaked at day 5, and suddenly decreased at day 7, except for osteopontin. Taken together with these results, the expression patterns of bone matrix-related genes during the later stages might be related to osteoclast activity. Additionally, the constant expression of Runx2 during bone formation and resorption suggested that osteoprogenitor cells always exist in the bone marrow cavity. Therefore, the expression patterns of these genes and the characteristics of bone matrix might extremely be related to the quick remodeling of medullary bone. PMID:22711567

High-signal T2-weighted bone marrow changes can be found in both bone marrow edema and hematopoietic marrow and are often seen on pediatric MR images of the feet and ankle. To evaluate whether high-signal T2 changes of the bone marrow seen on pediatric MRI of feet and ankles represent residual hematopoietic marrow. A total of 402 bones in 41 pediatric MRI studies of feet and ankles (34 children, 1-18 years) were reviewed by two observers who were blinded to the patients' ages. The studies were reviewed for the presence of high-signal changes of the bone marrow on sagittal fluid-sensitive images. The frequency and location of these foci were correlated with the patients' ages. High-signal T2 changes of the bone marrow were seen in 45/402 bones (11%) and in 24/41 patients younger than 16 years (59%). The changes were most commonly located in the calcaneus (54%), followed by the talus (35%) and navicular bone (35%), invariably at the endosteal surface. In 16 ankles, such foci were seen in the feet but not in the distal tibia/fibula. Symmetric presence (two ankles) or absence (four ankles) of high-signal marrow were seen in six of seven patients with bilateral ankles. High-signal T2 changes of the bone marrow in pediatric feet and ankle MRIs have a symmetric, fairly consistent pattern and disappear after the age of 15 years. We believe that these high-signal areas are normal and represent residual hematopoietic marrow. (orig.)

Summary Balicatib, an inhibitor of the osteoclastic enzyme cathepsin K, was tested in ovariectomized monkeys, a model for osteoporosis. As expected, ovariectomy-induced bone mass changes were partially prevented by balicatib treatment. Bone turnover was significantly decreased at most sites, but unlike most bone resorption inhibitors, periosteal bone formation rates were increased. Introduction Selective inhibitors of the osteoclastic enzyme cathepsin K have potential in osteoporosis treatment. This study evaluated the efficacy of balicatib (AAE581), a novel inhibitor of human cathepsin K, on bone mass and dynamic histomorphometric endpoints in ovariectomized monkeys. Methods Eighty adult female Macaca fascicularis underwent bilateral ovariectomies and were dosed twice daily by oral gavage...

Age-related changes of the femoral bone mass in several strains of the senescence-accelerated mouse (SAM) were investigated. Microdensitometrically, all strains exhibited essentially the same patterns of age changes, that is, bone mass corrected by the diameter of the shaft reached the peak value wh...

It is important to determine the changes in alveolar bone during periodontal treatments. At present, radiography is widely used to determine the changes. But small changes in alveolar bone cannot be detected on X-ray films. To detect these small changes, a direct observation system using gamma-ray from 133Ba was considered. Using a multi-channel analyzer, gamma-ray absorption through the bone was detected in this method. This method was compared with densitometric measurement on the films using sliced animal bone. The newly developed method detected the bone changes more accurately. To evaluate the influence of soft tissue, Mix-D was used in both measurements. 133Ba absorptiometry showed that soft tissue did not influence the measurement more than the densitometric method. PMID:2133683

Purpose: The aim of this study was to determine whether it was possible to differentiate septic from aseptic post-operative discitis in the lumbar spine by means of MR imaging. Material and Methods: The study was a retrospective evaluation of 12 patients with prior lumbar discectomy and suspected post-operative discitis displaying low-back pain and typical MR findings. Six patients had elevated serum C-reactive protein (CRP) (septic) and 6 had normal CRP (aseptic). We used MR imaging to assess the distribution and degree of changes in the disc, in adjacent bone marrow, and in surrounding soft tissue. Results: Of the 6 patients with increased CRP levels, 3 had extensive MR changes typical of septic post-operative discitis: 1 found soon after surgery; 2 found later. The other 3 patients with septic discitis, who were examined in the early post-operative period, showed MR changes similar to those in the 6 patients with aseptic discitis. Conclusion: Suspicion of septic post-operative discitis should be confirmed by MR imaging, serum CRP, and disc puncture. MR imaging is not reliable as the sole method for distinguishing septic from aseptic discitis in the early postoperative stage. (orig.).

Skeletal homeostasis is maintained by spatially coupled and balanced processes of osteolysis and osteogenesis. Several factors across the breast cancer continuum (e.g., adjuvant therapies, bone metastases in advanced disease) can disrupt this balance. Circulating levels of specific biochemical markers released during bone turnover provide relatively non-invasive means to assess ongoing rates of skeletal metabolism. Such markers may provide insight into the risk of bone loss and fractures in women with osteoporosis and during adjuvant therapy for breast cancer. In addition, bone marker levels and alterations might reflect tumor-bone interactions and response to bisphosphonate treatment in patients with bone metastases. Thus far, the largest body of evidence supports a potential role for urinary N-terminal cross-linked telopeptide of type I collagen (NTX) in predicting risks of skeletal morbidity and death, and monitoring response during zoledronic acid treatment, in patients with bone metastases. Other possible applications for bone markers include diagnosis of bone metastases and monitoring bone disease progression. Ongoing clinical trials evaluating the potential for bone marker changes to provide insights into the disease course and response to various classes of antiresorptive therapies are expected to expand the role of bone markers in the management of patients with breast cancer. PMID:22142664

This paper is based on the skeletal changes which were found in six cases with confirmed tuberous sclerosis. The bone changes of this rare condition are summarised. The differential diagnosis is discussed.

Reactivity transients have been analyzed with an updated RELAPS-3D (ver. 2.4.2) system model of the pin core design for the 2400MWt gas-cooled fast reactor (GCFR). Additional reactivity parameters were incorporated in the RELAP5 point-kinetics model to account for reactivity feedbacks due to axial and radial expansion of the core, fuel temperature changes (Doppler effect), and pressure changes (helium density changes). Three reactivity transients without scram were analyzed and the incidents were initiated respectively by reactivity ramp, loss of load, and depressurization. During the course of the analysis the turbine bypass model for the power conversion unit (PCU) was revised to enable a better utilization of forced flow cooling after the PCU is tripped. The analysis of the reactivity transients demonstrates the significant impact of the PCU on system pressure and core flow. Results from the modified turbine bypass model suggest a success path for the GCFR to mitigate reactivity transients without scram.

In addition to the examination of clinical signs, several laboratory markers have been measured for diagnostics and monitoring of pediatric septic bone and joint infections. Traditionally erythrocyte sedimentation rate (ESR) and leukocyte cell count have been used, whereas C-reactive protein (CRP) h...

It is well established that vascularization is required for effective bone healing. This implies that blood flow and interstitial fluid (ISF) flow are required for healing and maintenance of bone. The fact that changes in bone blood flow and ISF flow are associated with changes in bone remodeling and formation support this theory. ISF flow in bone results from transcortical pressure gradients produced by vascular and hydrostatic pressure, and mechanical loading. Conditions observed to alter flow rates include increases in venous pressure in hypertension, fluid shifts occurring in bedrest and microgravity, increases in vascularization during the injury-healing response, and mechanical compression and bending of bone during exercise. These conditions also induce changes in bone remodeling. Previously, we hypothesized that interstitial fluid flow in bone, and in particular fluid shear stress, serves to mediate signal transduction in mechanical loading- and injury-induced remodeling. In addition, we proposed that a lack or decrease of ISF flow results in the bone loss observed in disuse and microgravity. The purpose of this article is to review ISF flow in bone and its role in osteogenesis.

Changes in molecular texture and structure of isolated radioulnar bones of subadult European moose collected in various environmental pollution areas of Finland were investigated by using HNDT and x-ray diffraction methods. By using small caudo-cranial bending forces, the bones were tested by using HNDT. For bone molecular texture and structure studies by using x-ray diffraction methods, samples were taken from the ulnar metaphyse (Olecranon). Results show that the bones obtained from the Harjavalta area and one from North Karelia showed changes in molecular texture and structure compared with samples from apparently normal animals.

Findings of bone scintigraphy with /sup 99m/Tc-MDP were compared with bone radiography and biochemical data including total acid phosphatase (T. ACP), prostatic acid phosphatase (P. ACP), and alkaline phosphatase (ALP) in 35 patients with histologically proven prostatic cancer. Bone metastases were diagnosed in 20 of 35 cases (57%) by scintigraphy. The common sites of metastases were the pelvic bones, ribs, lumbar and thoracic vertebrae. In vertebrae, metastases were mainly distributed in the lower level. The most frequent radiographic change due to metastases was the osteoblastic type. On follow-up studies, there was a relatively good agreement in the results of bone scintigraphy and radiography. However, there was a good number of cases showing discrepancy between either scintigraphy or radiography and laboratory data. Bone scintigraphy seems to be the most contributory in monitoring bone metastases from prostatic cancer.

Water is commonly removed from bone to study its effect on mechanical behaviour; however, dehydration also alters the bone structure. To make matters worse, measuring structural changes in cancellous bone is complicated by a number of factors. Therefore, the goals of this study were to address these issues by (1) comparing Archimedes' method and a helium pycnometer as methods for measuring cancellous bone volume; (2) measuring the apparent dimensional and volumetric tissue shrinkage of cancellous bone at two levels of dehydration; and, (3) identifying whether a size effect exists in cancellous bone shrinkage. Cylindrical specimens (3, 5 and 8.3mm diameters) of cancellous bone were taken from the distal bovine femur. The apparent dimensions of each cylindrical specimen were measured in a fu...

This paper is a summary of the published studies on the possible association between osteoporosis and alveolar bone loss. Osteoporosis and low bone mass are considered as a major public health problem. The mandible like other bones of the body has a series of anatomical landmarks that can serve as radiographic indicators. Using these indicators it is possible to evaluate changes in bone with respect to its quantity or quality by different methods of taking images. Higher bone resorption was detected in women with a higher number of pregnancies. Also, the higher educated the patient, the less bone resorption. Women with a background of backaches had more bone resorption to those who did not have this backache background. Finally, it was recognized that it would be possible to clear the qual...

Changes in bone mineral mass were investigated by /sup 125/I-photon absorptiometry in 5 groups of patients; postmenopausal osteoporosis (n=50), after partial or total gastrectomy (n=54), thyroid disorders (n=28), parathyroid disorders (n=6) and healthy subjects (n=214) as control. Radial bone mineral content (BMC) was measured at the distal 1/3 and 1/6 sites of the radius and the densitometric patterns were analyzed. The results obtained were as follows: 1) Age variation in bone mineral mass and bone mineral change in pathological status were more sensitively detectable at the distal 1/6 site of the radius (predominantly trabecular) than the distal 1/3 site of the radius (predominantly cortical). 2) In osteoporosis there was a diminution in radial 1/6 BMC and a significant decrease of radial trabecular bone index (RTBI) estimated from densitometric patterns, as compared with age-matched control. Sequential changes of bone mineral mass were evaluated during the treatment. There was no significant change in bone mineral mass during the first 3 months of 1..cap alpha..-OH-D/sub 3/ administration. Bone mineral mass then decreased about 20% in radial 1/6 BMC in the course of the treatment. An increase in bone mineral mass at the distal 1/6 site of the radius was revealed after 1 year treatment with 1..cap alpha..-OH-D/sub 3/. But at the distal 1/3 site of the radius only a little change in bone mineral mass was recognized during the treatment. 3) Total gastrectomy caused a significant deficit of radial BMC as compared to partial gastrectomy. 1..cap alpha..-OH-D/sub 3/ was also effective on bone mineral loss after gastrectomy. 4) Loss of radial 1/6 BMC occurred in hyperthyroidism (high turn over osteoporosis) but not in hypothyroidism. 5) Striking bone mineral loss was observed in hyperparathyroidism, which recovered after surgical treatment.

A remarkable property of bone remodeling is that osteoblasts form bone matrix exactly where and when osteoclasts have removed it. The bone remodeling compartment (BRC) canopies that cover bone surfaces undergoing remodeling, were proposed to be critical players in this mechanism. Here, we provide support to this hypothesis by analyzing the changes in prevalence of BRC canopies during the progress of the remodeling cycle in a cohort of healthy individuals and in patients with endogenous Cushing's syndrome (CS), and by relating these changes in prevalence with the extent of bone forming surfaces. Both cohorts showed almost 100% canopy coverage above resorbing osteoclasts, and only about 76% above bone forming surfaces. This indicates that BRC canopies are invariably associated with the early stage of the remodeling cycle, but may disappear later. Interestingly, in control and two thirds of the CS patients, a significant decline in canopy coverage occurred only once bone formation was initiated, but in the remaining third of the CS patients the prevalence of canopies already decreased prior to bone formation. This canopy loss prior to initiation of bone formation coincided with significantly less bone forming surface compared to what did canopy loss at a later stage. These observations support a model where bone restitution is compromised in the absence of BRC canopies, and apparently does not start when the BRC canopy is lost prior to initiation of the bone formation step. This model is discussed in the context of possible biological roles of BRC canopies. It suggests that BRC canopies could be privileged targets for treating patients suffering from a negative bone formation-resorption balance. © 2011 American Society for Bone and Mineral Research.

Previously, bio-mechanical studies on the temporomandibular joint have concentrated mainly on the mandibular condyle while the articular eminence has been largely overlooked. Furthermore, research on the mechanical properties of bone using finite element analysis has focused on cortical bone in preference to cancellous bone. In this study, morphological changes in the internal structure of the articular eminence, as related to child growth, were examined using micro-computerized tomography (Micro-CT). Morphometric analysis of cancellous bone, representing both deciduous and early mixed dentitions, showed an increase in the bone volume fraction and trabecular thickness in the early mixed dentition. Finite element analysis indicated a directional transmission of stress. These results suggest that the morphology of the trabecular bone alters to adapt to the functional growth change from deciduous to early mixed dentition.   

Human aging is associated with bone loss leading to bone fragility and increased risk of fractures. The cellular and molecular causes of age-related bone loss are current intensive topic of investigation with the aim of identifying new approaches to abolish its negative effects on the skeleton. Age-related osteoblast dysfunction is the main cause of age-related bone loss in both men and women beyond the fifth decade and results from two groups of pathogenic mechanisms: extrinsic mechanisms that are mediated by age-related changes in bone microenvironment including changes in levels of hormones and growth factors, and intrinsic mechanisms caused by the osteoblast cellular senescence. The aim of this review is to provide a summary of the intrinsic senescence mechanisms affecting osteoblastic functions and how they can be targeted in order to abolish age-related osteoblastic dysfunction and bone loss associated with aging.

Mutations in DLX3 in humans lead to defects in craniofacial and appendicular bones, yet the in vivo activity related to Dlx3 function during normal skeletal development have not been fully elucidated. Here we used a conditional knockout approach to analyze the effects of neural crest deletion of Dlx3 on craniofacial bones development. At birth, mutant mice exhibit a normal overall positioning of the skull bones, but a change in the shape of the calvaria was observed. Molecular analysis of the genes affected in the frontal bones and mandibles from these mice identified several bone markers known to affect bone development, with a strong prediction for increased bone formation and mineralization in vivo. Interestingly, while a subset of these genes were similarly affected in frontal bones and mandibles (Sost, Mepe, Bglap, Alp, Ibsp, Agt), several genes, including Lect1 and Calca, were specifically affected in frontal bones. Consistent with these molecular alterations, cells isolated from the frontal bone of mutant mice exhibited increased differentiation and mineralization capacities ex vivo, supporting cell autonomous defects in neural crest cells. However, adult mutant animals exhibited decreased bone mineral density in both mandibles and calvaria, as well as a significant increase in bone porosity. Together, these observations suggest that mature osteoblasts in the adult respond to signals that regulate adult bone mass and remodeling. This study provides new downstream targets for Dlx3 in craniofacial bone, and gives additional evidence of the complex regulation of bone formation and homeostasis in the adult skeleton. J. Cell. Physiol. © 2012 Wiley Periodicals, Inc. PMID:22886599

The functional effects of bone and suture stiffness were considered here using finite element models representing three different theoretical phenotypes of an Alligator mississippiensis mandible. The models were loaded using force estimates derived from muscle architecture in dissected specimens, constrained at the 18th and 19th teeth in the upper jaw and 19th tooth of the lower jaw, as well as at the quadrate-articular joint. Stiffness was varied systematically in each theoretical phenotype. The three theoretical phenotypes included: (i) linear elastic isotropic bone of varying stiffness and no sutures; (ii) linear elastic orthotropic bone of varying stiffness with no sutures; and (iii) linear elastic isotropic bone of a constant stiffness with varying suture stiffness. Variation in the isotropic material properties of bone primarily resulted in changes in the magnitude of principal strain. By comparison, variation in the orthotropic material properties of bone and isotropic material properties of sutures resulted in: a greater number of bricks becoming either more compressive or more tensile, changing between being either dominantly compressive or tensile, and having larger changes in the orientation of maximum principal strain. These data indicate that variation in these model properties resulted in changes to the strain regime of the model, highlighting the importance of using biologically verified material properties when modeling vertebrate bones. When bones were compared within each set, the response of each to changing material properties varied. In two of the 12 bones in the mandible, varied material properties within sutures resulted in a decrease in the magnitude of principal strain in bricks adjacent to the bone/suture interface and decreases in stored elastic energy. The varied response of the mandibular bones to changes in suture stiffness highlights the importance of defining the appropriate functional unit when addressing relationships of performance and morphology. PMID:21091693

The hematological and pathological changes in lethally x-irradiated mice treated with isologous, homologous, or heterologous (rat) bone marrow are reported> Two different disease entities were observed in mice treated with homologous or heterologous bone marrow Bone marrow aplasia chiefly occurred before the 30th dav after irradiation. This resulted in death from septicemia or hemorrhage. The secondary bone marrow failure is explained by an immunological reaction of the host against the bone marrow graft. After the 30th postirradiation daily, the animals were emaciated and had dermatitis, pneumonia, diarrhea caused by focal colitis with crypt degeneration, and necrosis of the liver. The delayed foreign bone marrow reaction is of a complex nature. Impaired recovery of radiation-induced lesions, decreased resistance to bacterial infections, probabiy due to generalized atrophy of the lymphatic tissues, as well as an immunoligical reaction of the graft agained the hose are postulated to be causual facanimals treated with heterologous and those treated with homologous bone marrow. Bone marrow aplasia predominated in the mice of the former group. In contrast, the mice of the latter group were chiefly affected by pneumonia, diarrhea, and colitis. Regeneration of the lymphatic tissues occurred within a month after irradiation in animals treated with isologous bone marrow, but it was retarded or failed to occur in animals treated with foreign bone marrow. The possible relation of the lymphatic-tissue changes to the etiology of the secondary disease is discussed. (auth)

The purpose of this study was to examine the significance of increased bone density according to whether bone grafts were applied using demographic data with Cone Beam Computed Tomography (CBCT) and to compare the bone densities between before and after implant prosthesis using the Hounsfield index. Thirty-six randomly selected computed tomography (CT) scans were used for the analysis. The same sites were evaluated digitally using the Hounsfield scale with V-Implant 2.0TM, and the results were compared with maxillary posterior bone graft. Statistical data analysis was carried out to determine the correlation between the recorded Hounsfield unit (HU) of the bone graft and implant prosthesis using a Mann-Whitney U test and Wilcoxon Matched-pairs test. The bone grafted maxillary posterior teeth showed an increase in the mean values from-157 HU to 387 HU, whereas non-grafted maxillary posterior teeth showed an increase from 62 HU to 342 HU. After implantation, the grafted and non-grafted groups showed significantly higher bone density than before implantation. However, the grafted group showed significantly more changes than the non-grafted group. Bone density measurements using CBCT might provide an objective assessment of the bone quality as well as the correlation between bone density (Hounsfield scale) and bone grafts in the maxillary molar area.

This study was aimed to investigate the effects of ginsenoside Rg1 (Rg1) on hematopoietic function of bone marrow in cyclophosphamide-induced bone marrow depression mice. Mice were given cyclophosphamide (150mg/kg, i.p. for three days) to produce bone marrow depression. Rg1 was then administrated at 7.5 and 15mg/kg by i.p. for seven days. Bone marrow cells number was counted, and the percentage of hematopoietic stem cells (Lin(-)Sca-1(+)c-kit(+)) was quantified by flow cytometry. The histology of femoral bone was examined by H&E staining. The expression of calcium-sensing receptor mRNA was determined by the real time RT-PCR. Rg1 (7.5 and 15mg/kg) protected against cyclophosphamide-induced bone marrow depression, as evidenced by increased bone marrow cell numbers and improved femoral bone morphology. The percentage of Lin(-)Sca-1(+)c-kit(+) cells and lymphoid lineage CD3(+) cells were lower in cyclophosphamide group, but returned towards normal after Rg1 treatment in both bone marrow and peripheral blood cells. Expression of calcium-sensing receptor mRNA was increased in bone marrow cells on the 10th day after cyclophosphamide, but it was returned to normal level after Rg1 treatment. Rg1 alone did not produce these changes in normal mice. These results demonstrated that Rg1 improved hematopoietic function of bone marrow in cyclophosphamide-induced myelosuppression. PMID:22940261

Background Those receiving tenofovir/emtricitabine (TDF-FTC) had greater bone loss compared with abacavir/lamivudine (ABC-3TC) in a randomized simplification trial (STEAL study). Previous studies associated increased bone turnover and bone loss with initiation of antiretroviral treatment, however it is unclear whether change in bone mineral density (BMD) was a result of specific drugs, from immune reconstitution or from suppression of HIV replication. This analysis determined predictors of BMD change in the hip and spine by dual-energy x-ray absorptiometry in virologically suppressed participants through week 96. Methodology/Principal Findings Bone turnover markers (BTMs) tested were: formation [bone alkaline phosphatase, procollagen type 1 N-terminal propeptide (P1NP)]; resorption (C-terminal cross-linking telopeptide of type 1 collagen [CTx]); and bone cytokine-signalling (osteoprotegerin, RANK ligand). Independent predictors of BMD change were determined using forward, stepwise, linear regression. BTM changes and fracture risk (FRAX®) at week 96 were compared by t-test. Baseline characteristics (n?=?301) were: 98% male, mean age 45 years, current protease-inhibitor (PI) 23%, tenofovir/abacavir-naïve 52%. Independent baseline predictors of greater hip and spine bone loss were TDF-FTC randomisation (p?0.013), lower fat mass (p-trend?0.009), lower P1NP (p?=?0.015), and higher hip T score/spine BMD (p-trend?0.006). Baseline PI use was associated with greater spine bone loss (p?=?0.004). TDF-FTC increased P1NP and CTx through Wk96 (pBTM did not predict bone loss at week 96. No significant between-group difference was found in fracture risk. Conclusions/Significance Tenofovir/emtricitabine treatment, lower bone formation and lower fat mass predicted subsequent bone loss. There was no association between TDF-FTC and fracture risk. PMID:11295303

Using an ovariectomized (OVX) ovine model, we provide an analysis of the timing of changes in bone following estrogen deficiency. The expression of genes known to regulate osteoclastogenesis, matrix production, and mineralization, as measured by real-time RT-PCR, was significantly increased by 12 months; and increased expression was maintained through to 31 months post-OVX compared to controls. FTIR spectroscopy confirmed that mineralized crystals were less mature than in controls 12 months post-OVX and were even less so by 31 months. The mineral-to-matrix ratio was significantly reduced by 31 months, while the ratio of mature to immature collagen cross-linking was initially increased at 12 months and subsequently reduced at 31 months post-OVX. In contrast, trabecular number, thickness, and separation were unchanged at 12 months. Significant reductions in trabecular number and thickness and a significant increase in trabecular separation were observed 31 months after OVX. Most notably perhaps these combined changes led to a significant reduction in the compressive strength of trabecular bone after 31 months. The results indicate that there is an initial increase in bone turnover, which is accompanied by a change in bone composition. This is followed by a continued increase in bone resorption and relative reduction in bone formation, leading to deterioration in bone microarchitecture. Ultimately, these cumulative changes led to a significant reduction in the compressive strength of bones following 31 months of estrogen deficiency. These findings provide important insight into the time sequence of changes during osteoporosis. PMID:23076448

Demineralized allogenic bone implanted in the subcutis or muscle of rodents causes formation of heterotopic bone by osteoinduction. The osteoinductive response may be weaker in primates than in rodents. It was suggested that the osteoinductive response of demineralized bone for clinical use could be enhanced by using young donors, because studies have indicated that the osteoinductive response is reduced in demineralized bone of old versus young donors. However, these findings may not represent a gradual decline in the osteoinductive property of bone matrix throughout the life span. We evaluated quantitatively, by uptake of strontium 85, the osteoinductive effect of demineralized bone matrix from newborn, 8-week-old (adolescent), and 8-month-old (adult) male Wistar rats implanted in the abdominal muscles of 8-week-old male Wistar rats. The osteoinductive response increased significantly with increasing donor age. The results of the present study, weighed with those of previous studies, indicate that the osteogenic potential of the bone matrix increases from newborn to adulthood but decreases in the aged rat. This may be due to changes in concentration of essential growth factors (e.g., bone morphogenetic proteins) resulting from maturational changes from birth to adulthood and osteoporotic changes occurring in later years. The results do not support the contention that young donors of demineralized bone are preferable to adult donors.

Bone maintenance theory considers that the external load is the direct stimulating source of the bone remodeling. In this article, the method of experimental observation of self-repairing process of the bone defect and related results are introduced. Firstly, a hole was drilled in the rabbit thighbone so that the continuity of the bone was changed. Then bone defect model was established, and the thighbone data were obtained by using CT scanning, and the self-repairing process of bone defects caused by growth factor were observed and analyzed by MIMICS software. Finally, the relationship between volume changes of sclerotin was established, and scientific bases were provided for introducing the bionic topology optimization method to the remodeling process. The experimental results showed that the self-repairing of the each layer sclerotin of the young rabbits was faster than that of the adult ones under the same condition. In addition, the volume always changes contrarily between the spongy bone and enamel bone during the self-repairing process of bone defect. PMID:23016416

Biochemical bone turnover markers (BTMs) provide important information on the diagnosis, therapy and monitoring of metabolic bone diseases. They are evident before measurable changes in bone mineral density (BMD) take place. A total of 35 adult Saudi patients (23 males; 12 females) with type 2 diabetes and diagnosed to be vitamin D deficient were recruited in this prospective study. Here we investigated the effects of gender, season, and vitamin D status on bone biochemical markers of bone remodeling. Anthropometry and blood samples were collected at different intervals. Metabolic parameters and bone biomarkers were measured routinely and by ELISA. Both males and females had a significant increase in their vitamin D status over time, but no significant changes in the bone biomarkers were observed in females. In males there was a significant increase in circulating levels of corrected calcium and OPN (p = 0.004 and 0.01 respectively) and a significant decrease in crosslaps (p = 0.005). In all subjects there was a modest but significant positive relationship between vitamin D status and OC (R = 0.34; p = 0.04). In conclusion, our study demonstrates that changes in bone remodeling markers are affected by season, gender, and possibly vitamin D status. This gender difference may well reflect the physiologic pathway responsible for the higher peak bone mass achieved in males compared to females. PMID:22785268

A theoretical rationale, which could help in the investigation of mechanobiological factors affecting periprosthetic tissue healing, is still an open problem. We used a parametric sensitivity analysis to extend a theoretical model based on reactive transport and computational cell biology. The numerical experimentation involved the drill hole, the haptotactic and chemotactic migrations, and the initial concentration of an anabolic growth factor. Output measure was the mineral fraction in tissue surrounding a polymethymethacrylate (PMMA) canine implant (stable loaded implant, non-critical gap). Increasing growth factor concentration increased structural matrix synthesis. A cell adhesion gradient resulted in heterogeneous bone distribution and a growth factor gradient resulted in homogeneous bone distribution in the gap. This could explain the radial variation of bone density from the implant surface to the drill hole, indicating less secure fixation. This study helps to understand the relative importance of various host and clinical factors influencing bone distribution and resulting implant fixation.

Bone deformities caused by the chronic intake of large quantities of fluoride and the beneficial effect of calcium on its control have been studied for many years, but only limited data are available on the quantitative effect of fluoride intake and the beneficial impact of calcium on fluoride-induced changes in bone at the molecular level. It is necessary to determine the degree of fluoride-induced changes in bone at different levels of fluoride intake to evaluate the optimum safe intake level of fluoride for maintaining bone health and quality. The ameliorative effect of calcium at different dose levels on minimizing fluoride-induced changes in bone is important to quantify the amount of calcium intake necessary for reducing fluoride toxicity. Thirty rabbits, 2 months old, were divided i...

A novel biodegradable hydroxyapatite/chitosan-gelatin network (HA/CS-Gel) composite of similar composition to that of normal human bone was prepared as a three-dimensional biomimetic scaffold by phase separation method for bone tissue engineering. Changing the solid content and the compositional var...

Skeletal disorders of the foot can be assessed radiologically by changes in bone density, structure and/or form. The knowledge of specific morphological criteria is a precondition for differential diagnosis. Our classification of skeletal disorders of the foot is based on the specific signs that can be observed in systemic and local diseases affecting the pedal bones.

Bone undergoes continuous remodeling in response to mechanical loading. However, the underlying mechanisms by which bone cells respond to their changing mechanical environment, that is, strain in the load-bearing matrix or fluid flow through the canalicular network, are not well understood. It has b...

Objective Accumulating evidence suggests that statins might positively affect bone metabolism. In the present study, we compared the effect of rosuvastatin with that of ezetimibe on bone turnover markers in patients with type 2 diabetes mellitus as well as hypercholesterolemia. Design and Methods A total of 36 Japanese patients were enrolled in this open-label study and randomized to either rosuvastatin (2.5 mg/day) or ezetimibe (10 mg/day) groups at Shimane University Hospital. Bone turnover markers, such as bone-specific alkaline phosphatase, serum osteocalcin, urinary N-terminal telopeptide of type 1 collagen, and urinary deoxypyridinoline, were collected and compared between at baseline and at 3 months of treatment in each group. Results Background data was not significantly different between the two groups. Total cholesterol and LDL cholesterol levels were significantly decreased at 3 months in both groups. Serum osteocalcin levels in the rosuvastatin group were significantly increased with mean changes of 0.48 (95% confidence interval; 0.05 to 0.91, p=0.03), while no other bone marker in the ezetimibe group was changed. Changes in total cholesterol or LDL cholesterol levels were not significantly correlated with the changes in bone turnover markers. Conclusion Rosuvastatin may have a beneficial effect on bone metabolism in patients with type 2 diabetes and hypercholesterolemia by stimulating osteoblast function and bone formation, which seems to be independent of its cholesterol-lowering effect.   

Biochemical investigations into the pathogenesis of osteoarthritis have, for the last two decades, concentrated on the mechanisms involved in the destruction of the articular cartilage. Although bone changes are known to occur, the biochemistry of the collagenous matrix within osteoarthritic bone ha...

This patient represents a unique combination of multicentric osteomyelitis due to Klebsiella pneumoniae, lesions in the skull, pathological fracture of a long bone and no evidence of pulmonary disease. That Klebsiella pneumoniae osteomyelitis can occur in sickle cell anemia should be considered when such bone changes are seen. The remarkable resolution on conservative management also needs to be noted. (orig./GDG).

To review the clinical value of bone turnover markers (BTM), to initiate and/or monitor anti-resorptive treatment for osteoporosis compared with bone mineral density (BMD) and to evaluate suitable BTM and changes in BTM levels for significance of treatment efficiency. Consensus meeting generating gu...

This study investigated changes in bone integrity and circulating levels of insulin-like growth factor I (IGF-I) of hens subjected to two distinct molting regimens and fed pre- and post molt diets either high or low in omega-3 fatty acids (FA). A dual energy X-ray absorptiometer determined bone mine...

The earliest radiographic changes of osteomyelitis in the long bones is deep-seated edema manifesting as soft tissue swelling and obliteration of the intermuscular planes adjacent to the affected bone. Similarly, the early change of rib osteomyelitis is pericostal edema demonstrated by soft tissue swelling of the thoracic wall accompanied by an adjacent inward pleural displacement. In both osteomyelitis of the rib and the long bones, the bony changes will appear 1-2 weeks later. Pericostal edema can be readily diagnosed by ultrasound scan. Pericostal edema, although non specific and can occur in other conditions, yet it is a strong warning sign, set wihin the overall clinical picture of osteomyelitis.

Many environmental pollutants and drugs are toxic to the bone marrow. Some of these xenobiotics may initiate toxicity after undergoing bioactivation to free radicals and/or other reactive electrophiles. Peroxidases are a group of enzymes that catalyze the one-electron oxidative bioactivation of a variety of xenobiotics in vitro. Myeloperoxidase (MPO) is a peroxidative enzyme found in very high concentration in the neutrophils of human bone marrow. In this study, human MPO was evaluated to determine its ability to catalyze the in vitro bioactivation of known bone marrow toxicants that contain the aromatic hydroxyl (Ar-OH), aromatic amine (Ar-N-R{sub 2}), or heterocyclic tertiary amine ({double bond}N-R) moieties. The formation of free radical metabolites during the MPO-catalyzed bioactivation of hydroquinone and catechol (benzene metabolites), mitoxantrone and ametantrone (antitumor drugs), and chlorpromazine and promazine (antipsychotic drugs) was demonstrated by EPR spectroscopy. The reactivity of the products formed during the MPO catalyzed bioactivation of ({sup 14}C)hydroquinone and ({sup 14}C)catechol was shown by their covalent binding to protein and DNA in vitro. The covalently binding metabolite in each case is postulated to be the quinone form of the xenobiotic. In addition, both GSH and NADH were oxidized by the reactive intermediate(s) formed during the MPO-catalyzed bioactivation of many of the bone marrow toxicants tested. It was also shown that p,p-biphenol stimulated the MPO catalyzed bioactivation of both hydroquinone and catechol, while p-cresol stimulated the MPO-catalyzed bioactivation of catechol.

Repeated non-invasive measurements were performed in dogs to trabecular bone density (TBD), low density bone area (LDBA), and high density bone area (HDBA) in chronic arthritis using quantitative computed tomography (QCT). Unilateral chronic arthritis of the knee had been induced by weekly instillation of 2 ml carragheenin into the right knee joint for 12 weeks with the left knee serving as a control. CT scanning of the distal femoral condyles was performed in 12 mature dogs with chronic arthritis. Another 6 dogs underwent a longitudinal CT study starting immediately prior to induction of arthritis. Indentation test and histomorphometric analyses confirmed the bone density changes as measured by CT. (orig./GDG).

Elastic structure in cortical bone is usually simplified as orthotropic or transversely isotropic, which allows estimates of three dimensional technical constants from ultrasonic and density measurements. These elastic property estimates can then be used to study phenotypic changes in cortical bone structure and function, and to create finite element models of skeletal structures for studies of organismal variation and functional adaptation. This study examines assumptions of orthotropic or transversely isotropic material structure in cortical bone through the investigation of off axis ultrasonic velocities in the cortical plane in 10 samples each from a human femur, mandible and cranium. Longitudinal ultrasonic velocities were measured twice through each bone sample by rotating the perime...

Objectives: To describe the age-related changes of articular cartilage, subchondral bone morphology, and stiffness. Furthermore, to investigate whether subchondral bone histological and mechanical properties and meniscal histological properties are related to articular cartilage damage in the Dunkin Hartley guinea pig model of osteoarthritis (OA). Methods: Forty male Dunkin Hartley guinea pigs aged 2, 6, 9, and 12 months were studied. The right stifle joints and the left menisci were embedded undecalcified and the tibial articular cartilage and subchondral bone and the menisci were examined using histology. The stiffness of the left tibial subchondral bone was determined with indentation testing. Results: The Osteoarthritis Research Society International (OARSI) grade of the osteoarthritic...

The article reports on a 14-year old girl with periostal new formation of bones at the long bones of the lower arms, the femora and the lower legs the individual phalanges and metacarpalia after colitis ulcerosa which had lasted for several years and had progressed stagewise. After a clinically recorded new attack the periostal new formations of bone progressed. Some time after the last attack of colitis the periostal changes in the bones partially receded. The article discusses the hypothetic explanations aiming at interpreting the pathogenesis of hypertrophic osteoarthropathies and periostoses, as given in the literature.

This article aims at developing a new technology and instrument to explore the effect of gamma radiation on bone material. Exoelectron emission (EEE) phenomenon underlies a new electron spectroscopy to explore alteration of the electronic structurally dependence properties of bone material. The development of EEE technology for exploring the gamma radiation effects on bones is of high importance. Moreover, the influence of gamma radiation with different energies on the bone structure is discussed. It was found that the changes in EEE vary with radiation energy and radiation dose and that the response is non-linear. PMID:17643892

Bone metabolism is assessed using biochemical bone turnover markers (BTM). BTM reflect the metabolic effect of drugs on bone turnover, help to establish the lowest dose inducing the largest change in the BTM, predict treatment-related reduction in fracture risk, and are helpful in bridging studies. Changes in BTM during anti-osteoporotic therapy depend on the cellular mechanism of action of the drug, degree of change in bone turnover rate and route of administration. BTM help to establish the optimal dose of anti-osteoporotic drugs because treatment-related changes in BTM are more rapid compared with change in BMD. A greater decrease in BTM levels during the first year of tantiresorptive treatment is associated with greater antifracture efficacy over 3years. According to preliminary data, ...

Background Carbonated hydroxyapatite (CHA) and related calcium phosphates have been studied for many years as implant materials due to their similarity with the mineral phase of bone. The main limitation of CHA ceramics as well as other bioactive materials is that they have poor mechanical proprieties. It is thought that the mechanical device can cause an increase in metabolic activity and bone healing. In this study we investigated the reactivity and tissue behaviour of implanted CHA biomaterial reinforced by mini external fixator. Methods The evaluation of biomaterial biocompatibility and osteogenesis was performed on a rabbit model over a period of 6 weeks by radiological, histological and scanning electron microscopy (SEM) coupled with energy dispersive X-ray SEM-energy-dispersive X-ray (EDX) analysis. Results While rabbits treated with CHA exhibited more bone formation, and fibrous tissue was observed when empty bone defects were observed. EDX analysis detected little calcium and phosphorus on the surface of the bone that was not implanted, while high content of calcium (62.7%) and phosphorus (38%) was found on the interface bone cement. Conclusions Bone repairing showed that the mini external fixator stimulated the ossification which was pushed when grafted by CHA. This effect may play an important role in the prevention of implant loosening.

Purpose: People with spinal cord injury (SCI) experience bone loss and have an elevated rate of fracture in the paralysed limbs. The literature suggests an exponential time course of bone loss after SCI, but true rates may vary between patients. We propose systematic evaluation of bone status in the early stages of SCI to identify fast bone losers. Method: A case series of six patients with complete SCI were scanned using peripheral quantitative computed tomography within 5 weeks and at 4, 8 and 12 months post-injury. Bone mineral density (BMD) and bone mineral content (BMC) were measured at fracture-prone sites in the tibia and femur. Patient-specific-predictions (PSP) of expected rates of bone loss were produced by individualising published model equations according to each patient's measured values at baseline. Wilcoxon Signed-Rank tests were used to identify changes between time-points; chi-squared tests for differences between measured and PSP values. Results: In the lower limbs, mean values decreased significantly between baseline and 8 months post-injury, by 19-31% for trabecular BMD, 21-32% for total BMD, and 9-29% for BMC. Most subjects showed no significant differences between PSP and measured values, but individuals with significantly faster rates of bone loss than predicted should be investigated further. Conclusions: There was considerable intersubject variability in rates of bone loss after SCI. Patients showing the fastest bone loss could benefit from continued follow-up and possibly treatment. [Box: see text]. PMID:22553944

The influence of lead on the number of nucleated bone marrow cells and pluripotent stem cells in femur bone marrow was investigated in mice. It was found that neither a single nor 10 days' oral administration of lead at doses of 10-1,000 ..mu..g PbAc/kg b.w. led to any change in the bone marrow cellularity. After 1 month's oral administration of 1,000 ..mu..g PbAc/kg b.w., on the other hand, there was a significant reduction of nucleated bone marrow cells and pluripotent stem cells in the femur bone marrow of up to 20% in comparison with controls. Within 14 days after completing the lead administration, however, normal values in the bone marrow cellularity were found again. Three months' oral administration of lead at doses of 100 and 1,000 ..mu..g PbAc/kg b.w. led to a significant reduction in nucleated bone marrow cells and pluripotent stem cells in the femur bone marrow of up to 28% compared with the controls. In contrast to the experiments with 1 month's oral administration of lead the regeneration of the bone marrow was not completed 14 days after completing the administration of the lead. These results show that lead at doses above 100 ..mu..g PbAc/kg b.w. causes on long-term administration a clear reduction of the nucleated bone marrow cells combined with a depressed regeneration ability of the pluripotent stem cells.

Bone mass at all ages of the individuals is the integration of genetic factors, nutrition, physical exercise, hormonal environments, and other factors influencing the bone. It is also a measurable risk factor for osteoporosis which may subsequently cause bone fractures. Thus measuring bone mass is required to predict the probability of developing bone fractures subsequent to osteoporosis, and to diagnose osteoporosis, and to manage the osteoporosis patient. This paper discusses bone mineral measurements according to their characteristics and clinical application. Methodology for measuring bone mass has rapidly progressed during the past 15 years, which covers photodensitometry, photon absorptiometry (single energy X-ray absorptiometry and dual energy X-ray absorptiometry), quantitative CT, and ultrasound. These techniques have allowed noninvasive measurement of bone mineral density in any site of the skeleton with high accuracy and precision, although a single use of the technique cannot satisfy the complete clinical requirements. Thus the most appropriate method for measuring bone mineral density is important to monitor bone mass change and according to the specific site. (N.K.).

Burn and disuse results in metabolic and bone changes associated with substantial and sustained bone loss. Such loss can lead to an increased fracture incidence and osteopenia. We studied the independent effects of burn and disuse on bone morphology, composition and strength, and microstructure of the bone alterations 14days after injury. Sprague-Dawley rats were randomized into four groups: Sham/Ambulatory (SA), Burn/Ambulatory (BA), Sham/Hindlimb Unloaded (SH) and Burn/Hindlimb Unloaded (BH). Burn groups received a 40% total body surface area full-thickness scald burn. Disuse by hindlimb unloading was initiated immediately following injury. Bone turnover was determined in plasma and urine. Femur biomechanical parameters were measured by three-point bending tests and bone microarchitecture was determined by micro-computed tomography (uCT). On day 14, a significant reduction in body mass was observed as a result of burn, disuse and a combination of both. In terms of bone health, disuse alone and in combination affected femur weight, length and bone mineral content. Bending failure energy, an index of femur strength, was significantly reduced in all groups and maximum bending stress was lower when burn and disuse were combined. Osteocalcin was reduced in BA compared to the other groups, indicating influence of burn. The reductions observed in femur weight, BMC, biomechanical parameters and indices of bone formation are primarily responses to the combination of burn and disuse. These results offer insight into bone degradation following severe injury and disuse. PMID:23142361

Kidney transplantation, the most effective treatment for the metabolic abnormalities of chronic kidney disease (CKD), only partially corrects CKD-mineral and bone disorders. Posttransplantation bone disease, one of the major complications of kidney transplantation, is characterized by accelerated loss of bone mineral density and increased risk of fractures and osteonecrosis. The pathogenesis of posttransplantation bone disease is multifactorial and includes the persistent manifestations of pretransplantation CKD-mineral and bone disorder, peritransplantation changes in the fibroblast growth factor 23-parathyroid hormone-vitamin D axis, metabolic perturbations such as persistent hypophosphatemia and hypercalcemia, and the effects of immunosuppressive therapies. Posttransplantation fractures occur more commonly at peripheral than central sites. Although there is significant loss of bone density after transplantation, the evidence linking posttransplantation bone loss and subsequent fracture risk is circumstantial. Presently, there are no prospective clinical trials that define the optimal therapy for posttransplantation bone disease. Combined pharmacologic therapy that targets multiple components of the disordered pathways has been used. Although bisphosphonate or calcitriol therapy can preserve bone mineral density after transplantation, there is no evidence that these agents decrease fracture risk. Moreover, bisphosphonates pose potential risks for adynamic bone disease. PMID:23102732

Stress shielding from the presence of a femoral component can cause adverse changes to cortical bone geometry and porosity leading to increased fracture risk in the periprosthetic cortical bone. The objectives of this study were to determine if porosity increased after total hip arthroplasty along the principal axes, and to determine if a relationship existed between cortical bone porosity and geometry. Ten postmortem donors allowed comparisons of implanted femurs to the contralateral nonimplanted femurs. Transverse cross-sections of the femur were taken at 25, 45, 65, and 85% along the length of the femoral component. The cortical bone principal axes' location (degrees) and rigidity values (mm(4)) were based on cortical bone geometry by using digitized images of the cortical bone cross-sections. Percent porosity was measured along the principal axes using backscatter electron imaging. Cortical bone porosity increased in the more distal sections of the implanted femurs by approximately 3%, but did not preferentially increase along a particular principal axis. No correlation was found between changes in porosity and rigidity values. In conclusion, the porosity increases in the implanted femurs may have regionally reduced cortical bone strength. The locations of higher porosity did not appear related to the cortical bone geometry. PMID:18085646

The skeleton is the most common site for distant metastasis in patients with cancer. To detect bone metastasis and evaluate the efficacy of treatment, we usually use bone scintigraphy and check serum alkaline phosphatase (ALP). However, such evaluation is sometimes difficult due to flare phenomenon. A 61-year-old male was referred to our department with a suspected diagnosis of lung cancer. Following thorough examinations, he was diagnosed with primary lung cancer (adenocarcinoma, Stage IV) and found to have a mutation in the epidermal growth factor receptor gene at exon 21 (L858R). After initiating treatment with oral gefitinib, ALP increased and peaked at 3,592 U/L by 3 weeks and decreased thereafter. At 4 weeks following treatment initiation, bone scintigraphy revealed a marked increase in abnormal accumulation of 99mTc-polyphosphate, but the primary tumor and metastases in regions other than the bone were reduced. At 9 weeks after treatment initiation, abnormal accumulations was improved in bone scintigraphy, and computed tomography revealed osteoblastic changes consistent with the accumulated lesion observed by bone scintigraphy. After initiating cancer treatment for bone metastasis, it is not uncommon to observe transient asynchronous accumulation in bone scintigraphy or transient increases in ALP in patients who ultimately respond to the treatment. These changes are called flare phenomenon, and documented in patients with prostate cancer or breast cancer receiving treatment. When determining the efficacy of treatments that target carcinomas with bone metastases, it is important to note that flare phenomenon is often indistinguishable from disease progression indicators.   

During drilling of bone, excessive heat may cause thermonecrosis and this weakens the purchase of surgically placed screws and pins thus reduces the success of subsequent fixation and implantation process. In order to minimise the problems caused by high temperature (above 45degreeC) in bone drilling operations, it is necessary to operate with optimum cutting and drilling parameters. This study analysis the temperature changes during cortical bone drilling for different parameters such as drill rotation speed, feed-rate, drill diameter, drill force, bone mineral density and bone sex via the finite element method, FEM. The analysis have been validated by in vitro experiments using fresh calf cortical bones. Analytical and experimental results showed that the safe drilling parameters and dri...

This study investigated the feasibility of automatic image registration of MR high-spatial resolution proximal femur trabecular bone images as well as the effects of gray-level interpolation and volume of interest (VOI) misalignment on MR-derived trabecular bone structure parameters. For six subjects, a baseline scan and a follow-up scan of the proximal femur were acquired on the same day. An automatic image registration technique, based on mutual information, utilized a baseline and a follow-up scan to compute transform parameters that aligned the two images. These parameters were subsequently used to transform the follow-up image with three different gray-level interpolators. Nearest neighbor interpolation and b-spline approximation did not significantly alter bone parameters, while linear interpolation significantly modified bone parameters (pVOI along the slice (A/P) direction resulted in significant changes in bone parameters (pVOI alignment between baseline and follow-up images and does not compromise the integrity of MR-derived trabecular bone parameters.

The primary event of radiation damage to bone is atrophy and true necrosis of bone is uncommon. The postradiation atrophic changes of bone are the result of combined cellular and vascular damage, the former being more important. The damage to the osteoblast resulting in decreased matrix production is apparently the primary histopathologic event. Radiation damaged bone is susceptible to superimposed complications of fracture, infection, necrosis, and sarcoma. The primary radiographic evidence of atrophy, localized osteopenia, is late in appearing. Contrary to former views, the mature bone is quite radiosensitive and reacts quickly to even small doses of radiation. The differentiation of postirradiation atrophy and metastasis may be difficult. Biopsy should be the last resort because of the possibility of causing true necrosis in atrophic bone by trauma and infection.

IntroductionCone-beam computed tomography (CBCT) has been used to assess alveolar bone changes after rapid palatal expansion. The purpose of this study was to investigate the accuracy of alveolar bone-height measurements from CBCT images with varied bone thicknesses and imaging resolutions. MethodsEleven maxillary specimens from 6-month-old pigs were measured for alveolar bone height (distance between drilled reference holes and alveolar crests) at 6 locations with a digital caliper, followed by CBCT scanning at 0.4-mm and 0.25-mm voxel sizes. Buccal alveolar bone of these locations was then reduced approximately by 0.5 to 1.5 mm, followed by CBCT rescanning with the same voxel sizes. The CBCT images were measured by using 3-dimensional software to determine alveolar bone height and thickn...

Recently, it has been shown that transient bone biology can be observed in vivo using time-lapse micro-computed tomography (?CT) in the mouse tail bone. Nevertheless, in order for the mouse tail bone to be a model for human disease, the hallmarks of any disease must be mimicked. The aim of this study was to investigate whether postmenopausal osteoporosis could be modeled in caudal vertebrae of C57Bl/6?mice, considering static and dynamic bone morphometry as well as mechanical properties, and to describe temporal changes in bone remodeling rates. Twenty C57Bl/6?mice were ovariectomized (OVX, n?=?11) or sham-operated (SHM, n?=?9) and monitored with in vivo ?CT on the day of surgery and every 2?weeks after, up to 12?weeks. There was a significant decrease in bone volume fraction for OVX (?35%...

BACKGROUND: The effect of immunomodulator therapy (IMT) for multiple sclerosis (MS) on bone turnover is unknown. AIM: The aim of this study was to assess bone turnover in MS patients on IMT. METHODS: MS patients (n = 29) on maintenance IMT had repeat measurement of bone mineral density (BMD) after a 4.0 ± 0.4 years; bone turnover markers (BTM) were measured at the time of repeat BMD. RESULTS: BMD was unchanged at the spine but declined at the hip. BTMs, both resorption and formation, were reduced compared to normative range that may indicate an anti-resorptive action of IMT. Significant negative correlations were noted between BTMs and changes in BMD at spine but not hip. CONCLUSION: These observations suggest that IMT may have a beneficial effect on spinal bone by an antiresorptive action. A prospective study of the effect of IMT on BMD and bone turnover is warranted. PMID:22484845

Purpose: To evaluate whether initiation of running in sedentary individuals would lead to bone marrow edema on MR images, within the time span of 1 week. Materials and methods: The feet of 10 healthy volunteers were imaged by MR imaging before and after running during 30 min a day for 1 week. The images were evaluated by consensus of 2 musculoskeletal radiologists who graded the presence of bone marrow edema on a 4-point scale. Edema scores and number of bones involved before and after running were compared statistically. Results: Edema was present on the baseline images in 3 subjects. After running edema showed an increase or was present in 5 subjects. The changes after running were statistically significant. Bones involved were the talus, calcaneus, navicular bone, cuboid bone, and 5th metatarsal. Conclusion: Edema patterns can be seen in the feet of asymptomatic individuals. During initiation of running an increase of edema or development of new edema areas can be seen.

Decreased reactivity in mixed lymphocyte culture (MLC) was observed in patients within 1 yr after allogeneic and autologous bone marrow transplantation. Suppressor activity of peripheral blood mononuclear cells (PBMC) from transplant patients was studied by adding these cells as modulator cells to a bidirectional MLC with cells from normal individuals. PBMC from transplant patients markedly suppressed MLC reactivity in a dose-dependent manner. Suppressor activity was present in cells forming rosettes with sheep erythrocytes. Treatment of modulator cells with monoclonal antibodies against T cell differentiation antigens (OKT8, OKIa1) and complement completely abolished suppression of MLC. Suppressor activity was unaffected by 30 Gy irradiation. Suppressor activity declined gradually after transplantation and was inversely correlated with MLC reactivity of each patient at a significant level (p less than 0.01). These observations suggest that OKT8+ Ia+ radioresistant suppressor T cells play a role in the development of decreased MLC reactivity observed during the early post-transplant period.

Abstract Hydroxyapatite, the main inorganic material in natural bone, has been used widely for orthopaedic applications. Due to size effects and surface phenomena at the nanoscale, nanophase hydroxyapatite possesses unique properties compared to its bulk-phase counterpart. The high surface-to-volume ratio, reactivities, and biomimetic morphologies make nano-hydroxyapatite more favourable in applications such as orthopaedic implant coating or bone substitute filler. Recently, more efforts have been focused on the possibility of combining hydroxyapatite with other drugs and materials for multipurpose applications, such as antimicrobial treatments, osteoporosis treatments and magnetic manipulation. To build more effective nano-hydroxyapatite and composite systems, the particle synthesis proce...

Osseointegration is a complex process governed by the interaction of many cell types including blood cells (erythrocytes, platelets and leukocytes), phagocytic cells (macrophages) and bone cells (osteoblasts and osteoclasts) on or near the implant surface. The implant surface can be modified through a variety of methods in order to achieve control of some of these cellular interactions and consequently increase the degree of implant fixation with the surrounding bone tissue. In this investigation, titanium was coated with hydroxylated silica by plasma enhanced chemical vapour deposition (PECVD) to increase the surface hydrophilicity and generate reactive surface silanol groups. Subsequently, the silica-coated titanium surface was further modified through silanisation to generate surfaces b...

Potential complications after open wedge high tibial osteotomy (HTO) still remain unanswered as they are known to be primarily dependent on the surgical technique or the fixation strength. In this study, we evaluated the sensitivity of surgical variations (presence of bone graft, osteotomy line orientation and loading pattern) affecting post-operative stability using finite element analysis. Changes in stress distribution were also assessed at the lateral cortex bone and bone plate. A total six types of post-operative FE model were constructed to accommodate surgical variations based on the validated intact tibia model; Case 1 (lower level osteotomy, with no bone graft or with auto-tri-cortical bone), Case 2 (safe level osteotomy, with no bone graft or with auto-tri-cortical bone), Case 3 (upper level osteotomy, with no bone graft or with auto-tri-cortical bone). Two types of loading condition (axial compression_2450N with bending_240N and torsion_15Nm) were imparted. The use of bone graft material at the osteotomy site decreased the stress distribution at the lateral cortex bone and bone screw. And the lower level provided more post-operative stability than other osteotomy level (safe, upper). However, the ‘safe’ zone offered relatively similar results to those of the ‘lower’ zone. The osteotomy line near the lower end of the ‘safe’ zone was indeed the safest and most practical surgical approach as suggested in previous clinical studies. Therefore, our results suggested the use of bone graft with safe level osteotomy to assure the greatest post-operative stability and to reduce the likelihood of correction loss.   

The articular cartilage and the subchondral bone form a biocomposite that is uniquely adapted to the transfer of loads across the diarthrodial joint. During the evolution of the osteoarthritic process biomechanical and biological processes result in alterations in the composition, structure and functional properties of these tissues. Given the intimate contact between the cartilage and bone, alterations of either tissue will modulate the properties and function of the other joint component. The changes in periarticular bone tend to occur very early in the development of OA. Although chondrocytes also have the capacity to modulate their functional state in response to loading, the capacity of these cells to repair and modify their surrounding extracellular matrix is relatively limited in comparison to the adjacent subchondral bone. This differential adaptive capacity likely underlies the more rapid appearance of detectable skeletal changes in OA in comparison to the articular cartilage. The OA changes in periarticular bone include increases in subchondral cortical bone thickness, gradual decreases in subchondral trabeular bone mass, formation of marginal joint osteophytes, development of bone cysts and advancement of the zone of calcified cartilage between the articular cartilage and subchondral bone. The expansion of the zone of calcified cartilage contributes to overall thinning of the articular cartilage. The mechanisms involved in this process include the release of soluble mediators from chondrocytes in the deep zones of the articular cartilage and/or the influences of microcracks that have initiated focal remodeling in the calcified cartilage and subchondral bone in an attempt to repair the microdamage. There is the need for further studies to define the pathophysiological mechanisms involved in the interaction between subchondral bone and articular cartilage and for applying this information to the development of therapeutic interventions to improve the outcomes in patients with OA. PMID:22859924

Childhood central skull base masses are rare, often difficult to diagnose, and have overlapping imaging findings. In this review, we provide an overview of the epidemiology, clinical findings, and management of pediatric sphenoid bone and sphenoid sinus masses with an emphasis on imaging findings that may help to differentiate lesions. Radiologic-pathologic correlation is provided. Finally, an imaging-based algorithm is presented as a guide to help radiologists narrow their differential diagnoses. Some of the entities discussed are virtually unique to the pediatric population; others occur rarely in this age group but should be considered in the appropriate clinical setting. Entities included in the discussion are grouped into 2 categories: those that cause nonaggressive osseous remodeling and those that are more commonly associated with aggressive bone changes. Mucocele, aneurysmal bone cyst, giant cell lesions, meningioma, and fibrous dysplasia tend to remodel bone, while entities such as chordoma, craniopharyngioma, rhabdomyosarcoma, sinonasal carcinoma, and neuroblastoma may cause more aggressive local bone changes. PMID:20595365

Bone manifestations are frequent in Gaucher disease (GD), the most prevalent lysosomal storage disorder. Currently, therapy with enzyme replacement (ERT) or substrate reduction (SRT) is available. We investigated changes of laboratory parameters associated with bone metabolism in GD patients switching from ERT to SRT. Seven GD patients consecutively treated with ERT and SRT were studied. All patients had different degrees of bone involvement. Laboratory results were acquired at the time of change from ERT to SRT (0?months) and while on SRT (6?months, 12?18?months). Markers of GD activity remained stable or showed statistically insignificant increases. Six patients had stable skeletal manifestations and reported no bone-associated symptoms. One patient presented progressive bone manifestati...

In a period of 6.5 years, acute leukaemia was diagnosed in 140 children at our hospital: 137 children had long bone radiographs and 45 patients had bone lesions. Eleven of the 115 patients who had skull radiographs had osteolytic lesions and another four had wide sutures. No patients had bone changes at relapse or at cessation of 3 years' successful therapy. In acute lymphoblastic leukemia, the frequence of osseous lesions tended to be higher in patients in sub-groups with a more favourable prognosis. The duration of remission and survival times were higher in patients with ''leukemic'' long bones than in those without them (p <0.10 and <0.05, respectively). Changes in the skull could not be related to the outcome. We found no abnormalities in the bones of the eight patients with acute non-lymphoblastic leukemia.

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... cycle, estrogen keeps bones healthy. It may also affect cholesterol levels, keep skin and arteries more elastic, ... changes Some people think that women are more moody, irritable, or depressed during menopause. There could be ...

Extracellular fluid volume will be decreased, intracellular fluid volume will be ... Dietary Intake Can Predict and Protect Against Changes in Bone Metabolism .... and high dietary iron on oxidative damage and antioxidant status in rat eyes ...

The averaged monthly decrement in bone mineral density (BMD) is 1.0-1.5% of ... or from Scanco (Xtreme-CT) have the required resolution; these technologies, ... of the femoral neck, raises the critically for assessing temporal changes in the ...

While prolonged bed rest is an excellent analog for bone loss and muscle ... immune cell subpopulations in the blood (phenotyping), isolation and stimulation of cultured ...... Will such a change lead to disease, or is it a transient subclinical ...

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... the skull, where enlarged bone can lead to headache and hearing loss. The spine, where Paget's can ... disease can produce a devastating effect on a patient's life, simply because their body changes. Sometimes the ...

Histological techniques were utilized for evaluating progressive changes in tibial compact bone in adult male monkeys during chronic studies of immobilization-associated osteopenia. The animals were restrained in a semirecumbent position which reduces nor...

The present article evaluates 26 cases with arterial occlusion and additional polyneuropathy in diabetes mellitus or chronic alcohol addiction. For comparison, a group of 30 patients with arterial occlusion without neutrologically detectable polyneuropathy were also evaluated. It is pointed out that the osseous changes in the foot bone region are due to the additionally existing polyneuropathy and cannot be explained alone by an avascular bone necrosis in arterial vascular occlusion. Changes in the sense of an arthropathy occur in our group of patients even in case of unilateral arterial occlusion, these changes occurring bilaterally in the foot bones; after reconstruction measures in the arterial vascular system, these arthropathic changes in the foot bones continue to advance in case of persisting polyneuropathy.

Prostate cancer (PCa) results from a multistep process. This process includes initiation, which occurs through various aging events and multiple insults (such as chronic infection, inflammation and genetic instability through reactive oxygen species causing DNA double-strand breaks), followed by a multistep process of progression. These steps include several genetic and epigenetic alterations, as well as alterations to the chromatin structure, which occur in response to the carcinogenic stress-related events that sustain proliferative signaling. Events such as evading growth suppressors, resisting cell death, enabling replicative immortality, inducing angiogenesis, and activating invasion and metastasis are readily observed. In addition, in conjunction with these critical drivers of carcinogenesis, other factors related to the etiopathogenesis of PCa, involving energy metabolism and evasion of the immune surveillance system, appear to be involved. In addition, when cancer spread and metastasis occur, the 'tumor microenvironment' in the bone of PCa patients may provide a way to sustain dormancy or senescence and eventually establish a 'seed and soil' site where PCa proliferation and growth may occur over time. When PCa is initiated and progression ensues, significant alterations in nuclear size, shape and heterochromatin (DNA transcription) organization are found, and key nuclear transcriptional and structural proteins, as well as multiple nuclear bodies can lead to precancerous and malignant changes. These series of cellular and tissue-related malignancy-associated events can be quantified to assess disease progression and management. PMID:22504875

Purpose. To evaluate the histopathological condition of the pulp in teeth with different levels of chronic periodontitis in humans. Methods. Twenty-five single-root nondecayed teeth were divided into three groups as follows: group 1, clinical attachment level (CAL) 3 to 4?mm and alveolar bone loss (BL) from 4 to 6?mm without reaching the tooth apex; group 2, CAL ? 5?mm and BL > 6?mm without reaching the tooth apex; group 3, CAL ? 5?mm and BL > 6?mm up to the tooth apex. Histological analyses were accomplished after laboratorial processing. Results. The mean of CAL was 3.2 ± 0.7?mm in group 1, 7.6 ± 2.0?mm in group 2, and 12.1 ± 2.8?mm in group 3, while for BL it was 4.8 ± 0.9?mm, 7.6 ± 2.2?mm, and 11.9 ± 2.1?mm, respectively. Histopathological data in the pulpal chambers were similar among the three groups showing normal aspects, and, the radicular pulps showed variable levels of reactive dentin, fibrosis, dystrophic mineralizations, atrophy, and mononuclear inflammatory infiltrate. Conclusions. Gradual progression of the chronic periodontitis led to changes in the histopathological aspects of the radicular pulp with progressive involvement. PMID:19782474

Abstract Background- Chagas- disease is a zoonosis caused by a protozoan agent, Trypanosoma cruzi. Patients undergoing immunosuppressive treatment due to organ transplant, malignancies, infections, or chemotherapy may reactivate a preexisting chronic or indeterminate Trypanosoma cruzi infection. Methods- We present two transplant patients who underwent reactivation of Chagas- disease with cutaneous manifestations after an augmentation in their immunosuppressive therapy. A 38-year-old man was hospitalized on day-69 after receiving an allogeneic bone marrow transplant; he developed multiple painful erythematous plaques with diffuse borders, confined to the right cheek, trunk, thigh, elbows, and feet. A 59-year-old woman with a 14-year history of Chagasic cardiomyopathy presented one-month af...

This paper deals with the results of a radiation study in 34 patients with the clinical manifestations of maxillofacial osteomyelitides. It describes the radiation semiotics of changes occurring in the bone and its surrounding soft tissues of the maxillofacial region in different phases of osteomyelitis. Comparative analysis of orthopantograms and images obtained by multislice spiral computed tomography revealed the benefits of the latter in detecting soft tissue changes and subtle bone alterations. PMID:22187905

To clarify the effects of a single injection of recombinant human granulocyte colony-stimulating factor (rhG-CSF) on bone, rhG-CSF (100, 1,000, and 5,000 ?g/kg) was subcutaneously given to 6-week-old rats, and the femur and tibia were evaluated histopathologically at 2, 4 and 7 days after the injection. A significant increase in WBC counts related to the major pharmacological activity of G-CSF was observed in the rhG-CSF-treated groups at 1 to 2 days after the injection. Bone changes were found only in rats treated with 5,000 ?g/kg of rhG-CSF. The development of bone changes lagged behind the increase in WBC counts, and the bone changes occurred at 4 and 7 days after the injection. At 4 days after the injection, accelerated osteoclastic bone resorption was observed in the metaphyseal spongy trabeculae of femur and tibia. At 7 days after the injection, a small amount of newly formed bone due to intramembranous ossification was seen in the metaphysis of femur. These results suggest that the higher dose of rhG-CSF may intrinsically induce bone changes with a particular histopathological nature in rats.   

Introduction: It is not known whether hyaluronan (HA) has any effect on the underlying subchondral bone tissues. This study was to investigate the effects of high molecular weight HA (1.5x106 Daltons) intra-articular injection on subchondral bone tissues. Methods: Fifty-six male guinea pigs (6.5 months of age) were randomly divided into 5 groups studied in a short-term and a long-term experimental period. All HA groups received intra-articular injection of HA 0.4 mg/kg/week for 5 weeks in both knee joints. HA-II received injection for additional 5 weeks; HA-III received no more injection; and the control groups received vehicle. After sacrifice, the left tibiae were harvested and micro-CT scanned, followed by mechanical testing and collagen and mineral determination. Results: The HA-treated groups had almost normal cartilage, whereas the control groups had typical osteoarthrosis (OA)-related cartilage degradation. In the short-term study, compared with the control group, HA-injection resulted in a significantly decreased subchondral plate volume fraction and plate thickness. HA-treated cancellous bone had significantly lower bone volume fraction, and typical rod-like structure. In the long-term study, these latter changes were more pronounced, with an additionally significant decrease in connectivity and bone surface density. HA groups had greater bone mineral concentration and mineral density, lower collagen to mineral ratio, and preserved the mechanical properties of cancellous bone. The effects of HA on cartilage and subchondral bone were maintained when HA treatment was discontinued. Discussion: Significant positive effects of high molecular weight HA on the articular cartilage and subchondral bone tissues were seen. HA protects against OA-related cartilage degradation to almost normal level, and effectively changes the subchondral bone tissue microarchitecture, collagen and mineral content and density without altering the mechanical properties of cancellous bone. The most striking features are the microarchitectural changes in the subchondral cancellous bone that lead to lower bone density and markedly rod-like structure, and thus reducing cartilage stress during impact loading. Still, the subchondral bone has a greater mineral concentration, and a lower collagen to mineral ratio, and thus preserves the mechanical properties of cancellous bone. Short-term HA is sufficient and early HA is needed for intervention of OA initiation and progression.

The development of bone densitometry has made it clear that there are discrepancies in bone density at various measurement sites in a given individual. This study examined the consistency of bone density measurements across various sites in a strain of laboratory mouse (senescence-accelerated mouse; SAM). A systemic evaluation of the bone density was performed by dual-energy X-ray absorptiometry (DXA) on SAMP6 (P6) mice, a strain with low peak bone density, as measured by microphotodensitometry of the femoral bones, whereas the SAMP2 (P2) and SAMR1 (R1) strains have high peak bone density. We modified Jilka's method to more comprehensively measure the whole body and additional regions of interest (ROIs; head, right foreleg, left foreleg, right hindleg, left hindleg, spine, and tail). The age-related changes in the total (whole-body) BMD showed a common pattern among the strains studied, and the peak value was seen at 4 months old. P6 showed the lowest peak BMD. A detailed comparison of the bone density between P6 and P2 at the age of 4 months revealed significantly lower regional BMD values for P6 in all seven ROIs. The strain difference in BMD could not be attributed to a difference in size. In conclusion, P6 mice showed low bone density not only in their femurs but also in the subregions and over their entire body. This strain can be potentially useful in the investigation of the genetic basis of senile osteoporosis. PMID:15108062

A unitary bioresorbable cage/core bone graft substitute consisting of a stiff cage and a softer core with interconnected porosity is offered for spinal arthrodesis. Polycaprolactone, PCL, was used as the matrix and hydroxyapatite, HA, and ?-tricalcium phosphate, TCP, were used in the formulation of the cage layer to impart modulus increase and osteoconductivity while the core consisted solely of PCL. The crystallinity, biodegradation rate (under accelerated conditions) and mechanical properties, i.e., the uniaxial compression, relaxation modulus upon step compression and cyclic compressive fatigue properties, of the co-extruded cage/core bone graft substitutes could be manipulated by changes in the concentration of HA/TCP in the cage layer. The cyclic fatigue behavior of the cage/core bone graft substitutes were also compared to the behavior of bovine vertebral cancellous bone characterized under similar testing conditions. The biocompatibility of the cage/core bone graft substitutes were assessed via in vitro culturing of human bone marrow derived stromal cells, BMSCs. The cell proliferation rates, time dependencies of the alkaline phosphates (ALP) activity and the expressions of bone markers, i.e., Runx2, ALP, collagen type I, osteopontin and osteocalcin, and the collected ?-CT images demonstrated the differentiation of BMSCs via osteogenic lineage and formation of mineralized bone tissue to indicate the biocompatibility of the cage/core bone graft substitutes. PMID:22179683

Understanding the mechanical features of cortical bone and their changes with growth and adaptation to function plays an important role in our ability to interpret the morphology and evolution of craniofacial skeletons. We assessed the elastic properties of cortical bone of juvenile and adult baboon mandibles using ultrasonic techniques. Results showed that, overall, cortical bone from baboon mandibles could be modeled as an orthotropic elastic solid. There were significant differences in the directions of maximum stiffness, thickness, density, and elastic stiffness among different functional areas, indicating regional adaptations. After maturity, the cortical bone becomes thicker, denser, and stiffer, but less anisotropic. There were differences in elastic properties of the corpus and ramus between male and female mandibles which are not observed in human mandibles. There were correlations between cortical thicknesses and densities, between bone elastic properties and microstructural configuration, and between the directions of maximum stiffness and bone anatomical axes in some areas. The relationships between bone extrinsic and intrinsic properties bring us insights into the integration of form and function in craniofacial skeletons and suggest that we need to consider both macroscopic form, microstructural variation, and the material properties of bone matrix when studying the functional properties and adaptive nature of the craniofacial skeleton in primates. The differences between baboon and human mandibles is at variance to the pattern of differences in crania, suggesting differences in bone adaption to varying skeletal geometries and loading regimes at both phylogenetic and ontogenetic levels. PMID:19927280

Putty form graft materials may have additional favourable effects when compared with particulate ones in periodontal bone defects. The purpose of this study was to assess clinical and also radiographic changes following application of (i) putty form demineralized bone matrix (DBM), (ii) particulate form DBM and (iii) open flap debridement (control), using modified curtain suturing technique in the treatment of interproximal suprabony (horizontal) defects. Twenty-five chronic periodontitis patients with 125 sites (radiologically >or=4 mm horizontal bone defect) were selected to participate in this triple-blind, split mouth, randomized, controlled clinical trial. Putty and particulate form DBM grafts were placed at experimental sites. Clinical measurements included probing depth (PD), relative attachment level (RAL), gingival recession and bone probing depth (BPD) were made at baseline and repeated 12 months after the operations. Standardized digital radiographs were also taken to measure radiographic bone level (RBL) at baseline and 12 months later to be compared in a software. Probing depth reductions and RAL gains were significantly improved in all treatment groups (P 0.05). Bone probing depth measurements indicated comparable significant bone gain in graft applied groups (P 0.05). The results of this study indicate that either putty or particulate DBM demonstrates similar enhancements in soft and hard tissue parameters. Applying putty or particulate form DBM results with slight bone formation when compared with open flap debridement in horizontal bone defects at 1-year post-operative examination according to BPD measurements. PMID:19453850

Denosumab is a fully human monoclonal antibody that neutralizes the activity of RANKL, leading to the inhibition of osteoclast maturation, bone-resorbing activity, and survival. Evaluation of trans-iliac crest bone biopsy specimens in the phase 3 pivotal fracture study with denosumab in postmenopausal women with osteoporosis showed evidence of reduced bone turnover at the tissue level in subjects receiving denosumab, and up to one-third of subjects did not have evidence of tetracycline labeling in trabecular or cortical bone. Discontinuation of denosumab therapy has demonstrated that the effects of denosumab are reversible, as assessed by biochemical markers of bone turnover (BTM) and BMD. The precise nature of changes that occur at the tissue level with denosumab discontinuation have not been explored. Fifteen subjects were enrolled in a cohort study to evaluate the effects of denosumab discontinuation at the tissue level. Subjects had discontinued osteoporosis treatment for a mean time of 25.1 months (range 21 to 29 months). Bone histomorphometry results were compared with results from placebo-treated women with osteoporosis in the denosumab phase 3 pivotal fracture bone biopsy substudy, and BTMs were compared with subjects' pretreatment values. The results of this study showed normal histology and bone remodeling similar to those observed in untreated postmenopausal women with osteoporosis. With treatment cessation, 100% of biopsy specimens had evidence of tetracycline labels. Biochemical markers were comparable to and highly correlated with pretreatment levels. These data confirm that the effects of denosumab on bone turnover at the tissue level are fully reversible. PMID:21735475

The objective of the following case reports was to assess whether mineralized bone replacement grafts (eg, xenografts and allografts) could be added to recombinant human bone morphogenetic protein-2/acellular collagen sponge (rhBMP-2/ACS) in an effective manner that would: (1) reduce the graft shrinkage observed when using rhBMP-2/ACS alone, (2) reduce the volume and dose of rhBMP-2 required, and (3) preserve the osteoinductivity that rhBMP-2/ACS has shown when used alone. The primary outcome measures were histomorphometric analysis of vital bone production and analysis of serial computed tomographic scans to determine changes in bone graft density and stability. Over the 6-month course of this investigation, bone graft densities tended to increase (moreso with the xenograft than the allograft). The increased density in allograft cases was likely the result of both compression of the mineralized bone replacement graft and vital bone formation, seen histologically. Loss of volume was greater with the four-sponge dose than the two-sponge dose because of compression and resorption of the sponges. Vital bone formation in the allograft cases ranged from 36% to 53% but, because of the small sample size, it was not possible to determine any significant difference between the 5.6 mL (four-sponge) dose and the 2.8 mL (two-sponge) dose. Histology revealed robust new woven bone formation with only minimal traces of residual allograft, which appeared to have undergone accelerated remodeling or rhBMP-2-mediated resorption. PMID:20228973

[Purpose] To develop a digital radiographic bone trabecular structure analyzing system and to applied it to mandible. [Methods] Structural change was simulated by removing spongy bone in human dried mandible. Using a morphological filter processing, the skeletal features were extracted from digital radiographic image data obtained by computed radiography before and after the removal of spongy bone. The skeletal volume, surface, thickness, number, separation, complexity, spacing continuity and connectivity on the skeletal binary images were determined by morphometric indices calculation, star volume analysis and node-strut analysis. Using these quantified skeletal feature parameters, a mapping sheet for the structural evaluation was produced. The correlation between the fluctuation rate of each parameter after the removal of spongy bone with respect to the value before the removal of spongy bone and simulated structural change was examined. [Results] The skeletal binary image data quantified sixteen skeletal feature parameters using morphometric indices calculation, star volume analysis and node-strut analysis. These parameters agreed with the theoretical fluctuation pattern in the simulated skeletal structure deterioration of the mandibular bone trabeculae. [Conclusion] Using a morphological filter and bone histomorphometry, the radiological bone-morphometric analyzing system is useful for the evaluation of the mandibular trabecular structure.   

Bone loss is not only a well-documented effect of spaceflight on astronauts, but also a condition that affects millions of men and women on Earth each year. Many countermeasures aimed at preventing bone loss during spaceflight have been proposed, and many have been evaluated to some degree. To date, those showing potential have focused on either exercise or pharmacological interventions, but none have targeted dietary intake alone as a factor to predict or minimize bone loss during spaceflight. The "Dietary Intake Can Predict and Protect against Changes in Bone Metabolism during Spaceflight and Recovery" investigation ("Pro K") is one of the first inflight evaluations of a dietary countermeasure to lessen bone loss of astronauts. This protocol will test the hypothesis that the ratio of acid precursors to base precursors (specifically animal protein to potassium) in the diet can predict directional changes in bone mineral during spaceflight and recovery. The ratio of animal protein to potassium in the diet will be controlled for multiple short (4-day) periods before and during flight. Based on multiple sets of bed rest data, we hypothesize that a higher ratio of the intake of animal protein to the intake of potassium will yield higher concentrations of markers of bone resorption and urinary calcium excretion during flight and during recovery from bone mineral loss after long-duration spaceflight.

The study of pathological changes of bone is an important task in diagnostic procedures of patients with metabolic bone diseases such as osteoporosis as well as in monitoring the health state of astronauts during long-term space flights. The recent availability of high-resolution three-dimensional (3D) imaging of bone challenges the development of data analysis techniques able to assess changes of the 3D microarchitecture of trabecular bone. We introduce an approach based on spatial geometrical properties and define structural measures of complexity for 3D image analysis. These measures evaluate different aspects of organization and complexity of 3D structures, such as complexity of its surface or shape variability. We apply these measures to 3D data acquired by high-resolution microcomputed tomography (µCT) from human proximal tibiae and lumbar vertebrae at different stages of osteoporotic bone loss. The outcome is compared to the results of conventional static histomorphometry and exhibits clear relationships between the analyzed geometrical features of trabecular bone and loss of bone density, but also indicate that the measures reveal additional information about the structural composition of bone, which were not revealed by the static histomorphometry. Finally, we have studied the dependency of the developed measures of complexity on the spatial resolution of the µCT data sets.

Bone marrow fibrosis and new bone formation were induced by Pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF) injection in the rat. We investigated time course changes of megakaryocyte counts, circulating platelet counts, transforming growth factor-?1 (TGF-?1) levels in the bone marrow and those in platelet-poor plasma (PPP) when rats were injected with PEG-rHuMGDF at a dose of 0.1 mg/kg. Additionally, ultrastructural analysis of the circulating platelet and the bone marrow was performed by electron microscope. PEG-rHuMGDF injection daily for 5 days caused a megakaryocyte hyperplasia on days 5-7[after the commencement of the treatment], myelofibrosis on days 7-10, and new bone formation on days 8-15. TGF-?1 levels in the extracellular fluid of the marrow, megakaryocyte numbers, TGF-?1 levels in the PPP, and circulating platelet counts increased by PEG-rHuMGDF injection, and reached to the maximum level on days 7, 7, 8, and 10, respectively. Ultrastructural analysis showed that circulating platelets had no prominent morphological changes in the PEG-rHuMGDF-treated rats on day 8, compared with vehicle-treated rats. Additionally, there were many platelets or fragments of megakaryocyte around mesenchymal cells, and those fragments deposited in the newly formed bone on day 10. These data suggested that myelofibrosis and new bone formation were induced by the increase of TGF-?1 levels derived from bone marrow megakaryocytes.   

Trabecular bone fracture is closely related to the trabecular architecture, microdamage accumulation, and bone tissue properties. Micro-finite-element models have been used to investigate the elastic and yield properties of trabecular bone but have only seen limited application in modeling the microstructure dependent fracture of trabecular bone. In this research, dynamic fracture in two-dimensional (2D) micrographs of ovine (sheep) trabecular bone is modeled using the cohesive finite element method. For this purpose, the bone tissue is modeled as an orthotropic material with the cohesive parameters calculated from the experimental fracture properties of the human cortical bone. Crack propagation analyses are carried out in two different 2D orthogonal sections cut from a three-dimensional 8 mm diameter cylindrical trabecular bone sample. The two sections differ in microstructural features such as area fraction (ratio of the 2D space occupied by bone tissue to the total 2D space), mean trabecula thickness, and connectivity. Analyses focus on understanding the effect of the rate of loading as well as on how the rate variation interacts with the microstructural features to cause anisotropy in microdamage accumulation and in the fracture resistance. Results are analyzed in terms of the dependence of fracture energy dissipation on the microstructural features as well as in terms of the changes in damage and stresses associated with the bone architecture variation. Besides the obvious dependence of the fracture behavior on the rate of loading, it is found that the microstructure strongly influences the fracture properties. The orthogonal section with lesser area fraction, low connectivity, and higher mean trabecula thickness is more resistant to fracture than the section with high area fraction, high connectivity, and lower mean trabecula thickness. In addition, it is found that the trabecular architecture leads to inhomogeneous distribution of damage, irrespective of the symmetry in the applied loading with the fracture of the entire bone section rapidly progressing to bone fragmentation once the accumulated damage in any trabeculae reaches a critical limit. PMID:18412508

HIV infection causes loss of CD4(+) T cells and type 1 interferon (IFN)-producing and IFN-responsive dendritic cells, resulting in immunodeficiencies and susceptibility to opportunistic infections, such as Pneumocystis. Osteoporosis and bone marrow failure are additional unexplained complications in HIV-positive patients and patients with AIDS, respectively. We recently demonstrated that mice that lack lymphocytes and IFN a/b receptor (IFrag(-/-)) develop bone marrow failure after Pneumocystis lung infection, whereas lymphocyte-deficient, IFN ?/? receptor-competent mice (RAG(-/-)) had normal hematopoiesis. Interestingly, infected IFrag(-/-) mice also exhibited bone fragility, suggesting loss of bone mass. We quantified bone changes and evaluated the potential connection between progressing bone fragility and bone marrow failure after Pneumocystis lung infection in IFrag(-/-) mice. We found that Pneumocystis infection accelerated osteoclastogenesis as bone marrow failure progressed. This finding was consistent with induction of osteoclastogenic factors, including receptor-activated nuclear factor-?B ligand and the proapoptotic factor tumor necrosis factor-related apoptosis-inducing ligand, in conjunction with their shared decoy receptor osteoprotegerin, in the bone marrow of infected IFrag(-/-) mice. Deregulation of this axis has also been observed in HIV-positive individuals. Biphosphonate treatment of IFrag(-/-) mice prevented bone loss and protected loss of hematopoietic precursor cells that maintained activity in vitro but did not prevent loss of mature neutrophils. Together, these data show that bone loss and bone marrow failure are partially linked, which suggests that the deregulation of the receptor-activated nuclear factor-?B ligand/osteoprotegerin/tumor necrosis factor-related apoptosis-inducing ligand axis may connect the two phenotypes in our model. PMID:22626807

To investigate the relationship of circulating biomarkers of inflammation (C-reactive protein [CRP], interleukin-6 [IL-6], and YKL-40), angiogenesis (vascular endothelial growth factor), cartilage turnover (C-terminal crosslinking telopeptide of type II collagen [CTX-II], total aggrecan, matrix metalloproteinase 3 [MMP-3], and cartilage oligomeric matrix protein [COMP]), and bone turnover (CTX-I and osteocalcin) to inflammation on magnetic resonance imaging (MRI) and radiographic progression in patients with axial spondylarthritis (SpA) beginning tumor necrosis factor a (TNFa) inhibitor therapy.

We describe two cases of tuberculous otitis media studied with high-resolution computed tomography (CT). Findings included extensive soft tissue densities with fluid levels in the tympanic cavity, the antrum, the mastoid and petrous air cells. Multifocal bony erosions and reactive bone sclerosis were seen as well. CT proved valuable for planning therapy by accurately displaying the involvement of the various structures of the middle and inner ear. However, the specific nature of the disease could only be presumed. (orig.)

We here report a case of idiopathic hypereosinophilic syndrome with prompt response to treatment with imatinib. The patient presented with chest pain, myalgias, fatigue and weakness. Blood tests and bone marrow examination revealed striking eosinophilia. Clonal or reactive disorders were excluded by a wide range of diagnostic examinations. Treatment with high-dosis corticosteroids and hydroxyurea had little effect. Additional treatment with imatinib resulted in prompt symptomatic improvement and full haematological remission within five days of therapy. PMID:18282461

A reverse mode liquid crystal (LC) display has been investigated. A driving voltage strongly depends on a morphology which changes by reactive mesogens, photo initiators and LCs. It becomes higher when the domain size of the liquid crystal and the particle of the polymer reactive mesogen are smaller.   

Regional and total bone mass were determined in three groups of women by photon absorptiometry of the distal radius (bone mineral content (BMC)) and total neutron activation analysis (total body calcium (TBCa)), respectively. There were three groups of patients: group A, osteoporotic women treated with a variety of pharmacologic agents; group B, osteoporotic women (controls) taking only calcium supplements; and group C, normal postmenopausal women. The mean TBCa and BMC were considerably higher in the postmenopausal women than in the osteoporotic women. The rate of change of bone mass in group C was -0.45%/yr and -0.9%/yr for the total skeleton and radius, respectively. Group B had no significant rate of loss, whereas group A demonstrated a significant increase in TBCa of 0.75%/yr with no change in the BMC of the radius. There were no significant between-subject correlations for the slopes (rates of change) of the two bone mineral measurements.

In vitro experiments were undertaken to investigate the effect of intraperitoneal (i.p.) inoculation of BCG cell walls attached to oil droplets (BCGcw) on mitogenic and alloantigenic responses of spleen and bone marrow cells. These in vitro studies demonstrated that: (1) spleen cells from BCGcw-immunized ACI rats had decreased responsiveness to Concanavalin A (Con A) and to alloantigenic stimulation, (2) depressed Con A reactivity could also be induced in Buffalo rat spleen cells by the i.p. inoculation of BCGcw, (3) normal ACI rats had suppressor cells in their bone marrow but not in their spleens, (4) BCGcw-immunized ACI rats demonstrated an increase in the suppressive activity of their bone marrow as early as 1 day after inoculation of BCGcw, while suppressor activity was found in the spleen as early as 2 days after BCGcw inoculation, (5) characterization of the BCGcw-induced splecnic suppressor cell demonstrated it to be adherent to plastic or nylon wool, radiation-resistant, and removed by treatment with carbonyl iron. These properties were consistent with the identification of the suppressor cell as a macrophage, (6) the Con A and mixed lymphocyte reactivities of normal spleen cells could be suppressed by the addition of the adherent spleen cell population from BCGcw-immunized ACI rats, and (7) the adherent suppressor cell from BCGcw-immunized rats suppressed Con A reactivity across a major histocompatability barrier.

Bone gluing is an attractive surgical technique; however, its use in patients is hampered by a variety of side effects. Therefore, it was the aim of this ethically approved study to evaluate a novel biodegradable b-Tri-Calciumphosphate (b-TCP, Cerasorb)-enhanced bone adhesive regarding its toxicity and biocompatibility in a rabbit model. Fifty healthy New Zealand White rabbits were assigned in the study (n = 21) and sham-operated control group (n = 29). In the study group, a cylindrical part (4.6 x 10.0 mm) of the proximal tibia and distal femur was removed, reimplanted, and bone adhesive was applied. Blinded physical examination and sampling for hematology, clinical chemistry, and acute phase proteins (haptoglobin, C-reactive protein (CRP)) was performed before surgery and after 12, 24, 4...

Objective: Bone morphogenetic proteins (BMPs) and vascular endothelial growth factor (VEGF) have been reported in many studies to play a major role in the communication between endothelial cells and osteoblasts. The inflammatory reaction and relative hypoxia at the site of bone injury are the first stages of the fracture repair. rhBMP-2 has been used extensively in spinal fusion and reconstruction of maxillofacial bone defects with main complication is the formation of seroma. The aim of this study was to test whether rhBMP-2 regulates the expression of the angiogenic and inflammatory mediators in pre-osteoblasts via generating reactive oxygen species (ROS). Methods: rhBMP-2 effect on angiogenesis and inflammatory genes was assessed using normal human osteoblasts (NHOst). Angiogenesis gene...

Abstract Reactive oxygen species (ROS) are involved in both bone and cartilage physiology and play an important role in the pathogenesis of osteoporosis and osteoarthritis. The present study investigated the effect of running exercise on bone and cartilage in heterozygous manganese superoxide dismutase (SOD2)-deficient mice. It was hypothesized that exercise might induce an increased production of ROS in these tissues. Heterozygous SOD2-deficient mice should exhibit an impaired capability to compensate, resulting in an increased oxidative stress in cartilage and bone. Thirteen female wild type and 20 SOD2++/-â????? mice (aged 16 weeks) were randomly assigned to a non-active wild type (SOD2++/++Con, n == 7), a trained wild type (SOD2++/++Run, n == 6), a non-active SOD2++/-â????? (SOD2++/-...

The findings in the first phase were as follows: 1. Both reductive (non-selective) alkylation and selective oxygen alkylation brought about an increase in liquefaction reactivity for both coals. 2. Selective oxygen alkylation is more effective in enhancing the reactivity of low rank coals. In the second phase of studies, the major findings were as follows: 1. Liquefaction reactivity increases with increasing level of alkylation for both hydroliquefaction and co-processing reaction conditions. 2. the increase in reactivity found for O-alkylated Wyodak subbituminous coal is caused by chemical changes at phenolic and carboxylic functional sites. 3. O-methylation of Wyodak subbituminous coal reduced the apparent activation energy for liquefaction of this coal.

OBJECTIVE: Our objective is to understand the biological and mechanical pathways linking cartilage, bone, and marrow changes in the progression of osteoarthritis (OA). The aim of the present study was to evaluate bone structure and composition within bone marrow edema-like lesion (BMEL) regions associated with knee OA. METHODS: Tibial plateau specimens (n = 18) were collected from 10 subjects with knee OA during total knee arthroplasty (TKA). Magnetic resonance (MR) imaging was used to identify BMEL and quantify metrics of cartilage composition. Micro-computed tomography (?CT) and high-resolution peripheral quantitative computed tomography (HR-pQCT) were used to quantify density and microstructure of the subchondral trabecular bone. Fourier transform infrared (FTIR) spectroscopy was used to quantify tissue composition. RESULTS: Trabecular bone within BMEL was higher in volume fraction, with more and thicker trabeculae that were more plate-like in structure compared to unaffected regions. BMEL trabecular tissue composition had decreased phosphate and carbonate content. Marrow infiltration by a fibrous collagen network and evidence of increased bone remodeling were present. Structural and compositional changes were specifically localized to regions underlying cartilage degradation. CONCLUSION: These results support the paradigm of focal interactions among bone, marrow, and cartilage in the progression of knee OA. Quantitative evaluation of tissue changes and interactions may aid in the understanding of disease pathophysiology and provide imaging markers for disease progression. PMID:23025926

The structure of human cortical bone evolves over multiple length-scales from its basic constituents of collagen and hydroxyapatite at the nanoscale to osteonal structures at nearmillimeter dimensions, which all provide the basis for its mechanical properties. To resist fracture, bone’s toughness is derived intrinsically through plasticity (e.g., fibrillar sliding) at structural-scales typically below a micron and extrinsically (i.e., during crack growth) through mechanisms (e.g., crack deflection/bridging) generated at larger structural-scales. Biological factors such as aging lead to a markedly increased fracture risk, which is often associated with an age-related loss in bone mass (bone quantity). However, we find that age-related structural changes can significantly degrade the fracture resistance (bone quality) over multiple lengthscales. Using in situ small-/wide-angle x-ray scattering/diffraction to characterize sub-micron structural changes and synchrotron x-ray computed tomography and in situ fracture-toughness measurements in the scanning electron microscope to characterize effects at micron-scales, we show how these age-related structural changes at differing size-scales degrade both the intrinsic and extrinsic toughness of bone. Specifically, we attribute the loss in toughness to increased non-enzymatic collagen cross-linking which suppresses plasticity at nanoscale dimensions and to an increased osteonal density which limits the potency of crack-bridging mechanisms at micron-scales. The link between these processes is that the increased stiffness of the cross-linked collagen requires energy to be absorbed by “plastic” deformation at higher structural levels, which occurs by the process of microcracking.

We report the changes in biochemical markers of bone formation during the first 6 months of teriparatide therapy in postmenopausal women with osteoporosis according to previous antiresorptive treatment. Prior therapy does not adversely affect the response to teriparatide treatment. Similar bone markers levels are reached after 6 months of treatment. INTRODUCTION: The response of biochemical markers of bone turnover with teriparatide therapy in subjects who have previously received osteoporosis drugs is not fully elucidated. We examined biochemical markers of bone formation in women with osteoporosis treated with teriparatide and determined: (1) whether the response is associated with prior osteoporosis therapy, (2) which marker shows the best performance for detecting a response to therapy, and (3) the correlations between early changes in bone markers and subsequent bone mineral density (BMD) changes after 24 months of teriparatide. METHODS: We conducted a prospective, open-label, 24-month study at 95 centers in 10 countries in 758 postmenopausal women with established osteoporosis (n?=?181 treatment-naïve) who had at least one post-baseline bone marker determination. Teriparatide (20 ?g/day) was administered for up to 24 months. We measured procollagen type I N-terminal propeptide (PINP), bone-specific alkaline phosphatase (b-ALP), and total alkaline phosphatase (t-ALP) at baseline, 1 and 6 months, and change in BMD at the lumbar spine, total hip and femoral neck from baseline to 24 months. RESULTS: Significant increases in formation markers occurred after 1 month of teriparatide regardless of prior osteoporosis therapy. The absolute increase at 1 month was lower in previously treated versus treatment-naïve patients, but after 6 months all groups reached similar levels. PINP showed the best signal-to-noise ratio. Baseline PINP correlated positively and significantly with BMD response at 24 months. CONCLUSIONS: This study suggests that the long-term responsiveness of bone formation markers to teriparatide is notaffected in subjects previously treated with antiresorptive drugs.