Osteoid Tissue Research Articles

Knee Pain in a 13-Year-Old Boy

Knee Pain in a 13-Year-Old Boy

Juxtacortical osteosarcoma of tibia from a medieval cemetery of Budapest

Juxtacortical osteosarcoma occurred on the right tibia and fibula of a 20-22 years old man found in a medieval period cemetery of Budapest. MACROSCOPIC DESCRIPTION: The tumor is located circumferentially on the midshaft of the tibia and fibula and appears cone-shaped. The lesion measured 160 mm in length and 3-5 mm in height. The surface of the tumor is irregular, rough, in some areas shows spicules. These spicules averaged 2-4 mm in length and 1-2 mm in diameter. The anterior and medial surface of the tibia is completely covered by osseous tumor. RADIOGRAPHY: The X-ray study demonstrates the medullary involvement, with mixed osteolytic and osteoblastic areas. Tumor infiltration of the cortex is also apparent as irregular rarefication and lytic lesions. In some areas a "sunburst" picture could be seen. The X-ray picture is characteristic for juxtacortical osteosarcoma. MICROSCOPIC EXAMINATION: stereomicroscopy of specimens shows a sponge-like structure of the surface. The cortical bone is completely destroyed and deep cavities are seen between spiculous and gyrificated neoplastic bone. The spiculae are varied in length and thickness. Irregular bulky bone trabeculae demonstrating uncontrolled neoplastic reaction could be detected. By light microscopic examination severe destruction, osteolytic lesions are seen both in the cortical bone and in the cancellous bone in the peripheral parts of the tumors. Within the neoplastic bone only few remnants of the primary (normal) bone structure could be demonstrated. No reparative reactions were seen next to the osteolysis, the collagen fibers and lamellas are destroyed. Beside the destruction of original bone larger structures composed of irregular newly built nepotistic bone trabeculae can be detected. The newly formed trabeculae (spiculae) contain a tumorous ground substance (probably osteoid tissue) with few collagen fibers, and these areas are covered with a thin bony lamella. In some areas the neoplastic structures are in intimate contact with the original cancellous bone remnants. IMMUNOHISTOCHEMISTRY: Both the osteosarcoma and chondrosarcoma show osteoid and bone neoformation while in the chondrosarcoma type II collagen could also detected. By immunohistochemical reactions no type II and III collagen, only type I collagen reaction was positive. This means that no cartilaginous tissues were present in the tumor. Scanning electron microscopy of these specimens shows sponge-like structures. The tumor reveals irregular trabecular and spicular texture,the spicules are various in diameter and in some spiculae rounded deposits attached to the surface. In our case we found typical radiological and histological picture of the juxtacortical osteosarcoma.

Extended bioactivity in the proximity of hydroxyapatite ceramic surfaces induced by polarization charges.

Surface charges of electrically polarized hydroxyapatite (HAp) ceramics were demonstrated to enhance osteoconductivity in the wide gap of the canine bone whereas the bone formation processes varied according to the charge polarity. Cell reactions in the vicinity of the charged surfaces of HAp ceramics were not phagocytic absorption but rather bone formation by stimulated osteoblasts surrounding newly formed bone 7 days after implantation. The bone formation in direct contact with negatively charged ceramic surfaces suggests that the negative charges enhanced the osteobonding ability of the HAp ceramics. In the vicinity of the positively charged HAp surface, the formation of bones derived from osteoid tissues entirely occupied the 0.2-0.3-mm gaps between the HAp and the bone at 7 days. Surface charges induced by electrical polarization significantly cooperated with the innate bioactivity of HAp and reconstructed the wide bone defects more promptly than did the nonpolarized HAp ceramic surface.

Primary mesenchymal chondrosarcoma of the lung

Mesenchymal chondrosarcoma has been well documented in the somatic soft tissue and bone. It is a rare subtype of chondrosarcoma characterized by the presence of islands of chondroid or by less osteoid tissue enmeshed within dense sheets of primitive small blue mesenchymal cells with hemangiopericytoma-like vessels, or by both. The vast majority of previously published pulmonary mesenchymal chondrosarcoma was metastatic. To the best of our knowledge, only one case of primary pulmonary mesenchymal chondrosarcoma has been described in the literature. Herein, we report the second case of primary mesenchymal chondrosarcoma of the lung and emphasize that biopsy may yield only nonspecific small blue cells, whereas a detailed evaluation of the resected specimen allows definite diagnosis of this rare lung tumor.

Periosteal hyperostosis (exostosis) in DBA/1 male mice.

Periosteal hyperostosis (exostosis) was identified in 5.9% (11/188) of DBA/1 male mice 10-14 weeks old used for collagen-induced arthritis (CIA) efficacy testing of immunomodulatory biologics. Mice with and without CIA in the affected limb, and also control and treated groups, were involved, with bilateral lesions in one mouse. Hyperostosis was characterized by circumferential and raised masses of variable location, length, and laterality, generally external to but occasionally breaching the periosteum of the metatarsals, metacarpals, tibia, femur, and humerus. Proportionally, the hyperostotic foci consisted of cancellous and woven bone, followed by osteoid, cartilage, and fibrous connective tissue and rarely inflammatory cells. A displaced, presumably pathological fracture with callus formation was a concurrent lesion in only one case. Tartrate-resistant acid phosphatase-positive cells were frequent at bony interfaces, indicating an active resorptive process. Periosteal hyperostosis is an incidental and potentially common finding in DBA/1 mice. Underreporting may occur due to the male bias in disease expression of this CIA model, sampling bias (generally paws only), tissue obliteration in the presence of CIA, and lack of comprehensive historical data on the background and aging lesions in this strain of mouse. Identification of such confounding bony lesions is important to the interpretation of efficacy studies, and suggests the need to further examine the biology of bone development in this strain of mouse.

Fluoride and strontium accumulation in bone does not correlate with osteoid tissue in dialysis patients.

Osteomalacia is now a rare disease in dialysis patients in developed countries since the withdrawal of aluminium overload. The involvement of fluoride and strontium in the pathogenesis of the disease has been suggested. The aim of this study was to investigate a possible association between osteomalacia in dialysis patients and the fluoride or strontium contents of bone. Of 271 bone biopsies from chronic haemodialysis patients referred to our centre, we studied the nine biopsies from patients with osteomalacia. They were compared with 23 biopsies from patients with hyperparathyroidism and 24 biopsies from patients with adynamic bone disease. Histomorphometric static and dynamic indices were measured. Bone fluoride and strontium contents were measured in biopsies from haemodialysis patients, and were compared with those of control patients. In the nine patients with osteomalacia, we found an absence of double labelled surfaces and increased osteoid thickness. Mild aluminium overload was observed in two of the nine patients. The bone strontium content of the entire dialysis population studied was not significantly different from control values (0.023+/-0.001 vs 0.019+/-0.002% mol/mol, P=0.15). However, bone strontium level was slightly but significantly increased in patients with osteomalacia (0.030+/-0.005%), compared with both controls (0.019+/-0.002%, P<0.05) and the other bone diseases (0.021+/-0.002%, P<0.05). Bone fluoride content was significantly higher in the entire dialysis population than in the controls (0.33+/-0.04 vs 0.13+/-0.018% (g/g ash weight), P=0.04). It was increased in osteomalacic patients compared with controls and with patients having hyperparathyroidism or adynamic bone disease. There was no correlation between formation indices (OV/BV, OS/BS, Ob.S/BS) and bone fluoride or strontium content. We found a prevalence of osteomalacia of 3.3% in our biopsy series for chronic dialysis patients. However, although bone strontium and fluoride contents were slightly increased, no causal relationship with these individual metals and osteomalacia could be firmly established in this small number of patients. The hypothesis of strontium- or fluoride-induced osteomalacia in renal patients merits further investigation.

COX-1 and COX-2 expression in osteoid osteomas

Osteoid osteoma is a benign bone forming neoplasm that is characterized by its small size (less than 2 cm), self-limited growth, and the tendency to cause extensive reactive changes in the adjacent tissue. The lesion classically presents with severe pain at night that is dramatically relieved by NSAIDs. The tumor has been shown to express very high levels of prostaglandins, particularly PGE2 and PGI2. The high local levels of these prostaglandins are presumed to be the cause of the intense pain seen in patients with this lesion. One generally accepted form of treatment is the prolonged use of NSAIDs. Since the cyclooxygenases are thought to be the source of these prostaglandins, and the central target of NSAIDs, we evaluated the expression of cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) in osteoid osteoma tissues from patients following surgery. In the 12 specimens examined we found that the tumor osteoblasts had strong immunohistochemical staining for COX-2, while the staining in the surrounding host osteoblasts in the reactive bone was scant. Significant COX-1 staining was also detected in both tumor and host osteoblasts. For comparison we examined the COX expression in human fracture callus, fibrous dysplasia, osteoblastoma, osteofibrous dysplasia, and myositis ossificans. With the exception of fracture callus, very limited amounts of COX-2 could be detected in these tissues. Taken together, we conclude that the increased production of prostaglandins by osteoid osteomas implicates that COX-2 is one of the mediators of this condition. These findings suggest that the newly selective COX-2 inhibitors could be used to more safely treat osteoid osteomas.

Alcoholism, hypercortisonism, fat embolism and osseous avascular necrosis. 1971.

Alcoholism, hypercortisonism, fat embolism and osseous avascular necrosis. 1971.

Patient and staff dose during CT guided biopsy, drainage and coagulation

Patient and staff dose during CT guided coagulation of osteoid osteoma, tissue biopsy and abscess drainage were evaluated retrospectively on a conventional CT scanner and prospectively on a scanner equipped with fluoroscopic CT. The computed tomography dose index (CTDI) and the individual dose equivalent, i.e. the penetrating dose for workers at a depth of 10 mm tissue, were measured. Evaluation of CTDI enabled effective dose and maximum skin entrance doses for the patient to be determined. Doses were assessed for 96 CT guided interventions, including 16 drainages with average effective doses of 13.5 mSv and 9.3 mSv for the conventional CT scanner and the scanner with spiral CT fluoroscopy, respectively, 49 biopsies (effective doses of 8 mSv and 6.1 mSv, respectively), and 31 coagulations of osteoid osteoma (effective doses of 2.1 mSv and 0.8 mSv, respectively). Effective doses to patients were in the same range as those observed for regular diagnostic CT examinations. Entrance skin doses were well below the 2 Gy threshold for deterministic skin effects on the CT scanner equipped with fluoroscopic function (0.03-0.33 Gy), whilst skin doses on the conventional scanner were considerably higher (0.09-1.61 Gy). This is mainly owing to the fact that on the conventional scanner mAs was rarely reduced for scans evaluating needle position whereas low mAs per rotation was selected on the scanner with the fluoroscopy option. The maximum dose to a worker measured outside the lead apron was 28 microSv for one single procedure. The mean dose per procedure was below 10 microSv for radiologists and below 1 microSv for radiographers. Correcting for attenuation of the lead apron, the doses to workers are very low.

The osteoblastic phenotype in calcium-depleted and calcium-repleted rats: a structural and histomorphometric study.

In a previous report we showed that young rats fed a calcium-free diet for 28 days developed severe hypocalcaemia and showed a significant increase in serum alkaline phosphatase activity. The main histological and cytochemical changes exhibited by these animals in bone of the metaphyseal primary spongiosa were: (1) hyperplasia of osteoblasts, (2) an increase in the frequency of tartrate-resistant acid phosphatase (TRAP)-positive osteoblasts apposed to osteoid, and (3) an excessive amount of osteoid tissue. In addition to typical osteoblasts, there was a subpopulation of osteoblast-like cells with coated pits, lysosome-like bodies and large cytoplasmic processes. In the present study, we investigated how the above parameters change when calcium-depleted rats are placed on a normal diet for 7 days. Such a regimen normalized calcium concentration and alkaline phosphatase activity in the serum. The osteoid thickness returned to normal and, in some areas, was fully calcified. Most osteoblasts no longer showed TRAP activity and their ultrastructure was similar to that found in controls. Despite an intense alkaline phosphatase activity, some of them still exhibited a number of macrophagic characteristics. They were TRAP-positive, and showed electron-dense bodies in the cytoplasm facing bone, an abundance of coated pits, calcified spicules impinging on the cell membrane and large processes extending into the mineralized matrix. We concluded that calcium deficiency causes hyperplasia of osteoblasts in primary spongiosa and an increase in expression of TRAP. It also induces changes in their phenotype characterized by the acquisition of macrophagic cellular features. While TRAP activity is normalized by calcium repletion, macrophagic characteristics persist. These results suggest that the osteoblast can modulate its phenotype according to its physiological status.

Selection and amplification of a bone marrow cell population and its induction to the chondro-osteogenic lineage by rhOP-1: an in vitro and in vivo study.

The differentiation and maturation of osteoprogenitor cells into osteoblasts are processes which are thought to be modulated by transforming growth factors-beta (TGF-beta) as well as by bone morphogenetic proteins (BMPs). Osteogenic protein-1 (OP-1, also known as BMP-7) is a member of the BMP family, and it is considered to have important regulatory roles in skeletal embryogenesis and bone healing. Rat bone marrow cells were cultured in vitro in a collagen-gel medium containing 0.5% fetal bovine serum (FBS) for 10 days in the presence of 40 ng/ml recombinant human OP-1 (rhOP-1). Under these conditions, survival of the bone marrow cell population was dependent on the presence of rhOP-1. Subsequently, the selected cells were cultured-for 6 days in medium containing 40 ng rhOP-1 and 10% FBS. During the last 2 days, dexamethasone (10(-8) M) and beta-glycerophosphate (2 mM) were added to potentiate osteoinduction. Concomitant with an up-regulation of cell proliferation, DNA synthesis levels, colony number and size were determined. Chondro-osteogenic differentiation in vitro was evaluated in terms of the expression of alkaline phosphatase, the production of osteocalcin and the formation of mineralized matrix. After culturing in vitro, cells were placed inside diffusion chambers or inactivated demineralized bone matrix (DBM) cylinders and implanted subdermically into the backs of old rats for 28 days. Biochemical, histological and immunocytochemical analyses provided evidence of cartilage and osteoid tissue inside the diffusion chambers, whereas bone was also observed inside the DBM implants. In conclusion, this experimental procedure is capable of selecting a cell population from bone marrow which, in the presence of rhOP-1, achieves skeletogenic potential under in vitro as well as in vivo environments.

Dedifferentiated liposarcoma with chondroblastic osteosarcomatous dedifferentiation

We describe a rare case of dedifferentiated liposarcoma with features resembling chondroblastic osteosarcoma in the dedifferentiated component. The tumor was removed from the left thigh in a 78-year-old male. It consisted of a well-differentiated liposarcoma and an anaplastic component that contained numerous osteoid and cartilaginous tissues surrounded by high-grade spindle cell sarcoma. To our knowledge, only two cases similar to the divergent chondroblastic osteosarcomatous dedifferentiation of this disease have been reported in the literature.

Activation of beta-catenin in epithelial and mesenchymal hepatoblastomas.

Wnt/beta-catenin signaling is frequently activated in cancer cells by stabilizing mutations of beta-catenin or loss-of-function mutations of the APC tumor suppressor gene. We have analysed the role of beta-catenin in the pathogenesis of hepatoblastoma (HB), an embryonic liver tumor occurring mainly in children under 2 years of age. Sequence analysis of the beta-catenin NH2-terminal domain in 18 epithelial and mixed HBs revealed missense mutations in the GSK3beta phosphorylation motif or interstitial deletions in 12 tumors (67%). In the remaining cases, no truncating mutation of APC could be evidenced. Immunohistochemical analysis of beta-catenin in 11 HBs demonstrated nuclear/cytoplasmic accumulation of the protein in all tumors analysed, with predominant nuclear beta-catenin immunostaining in undifferentiated cells. Membranous beta-catenin localization was preserved only in fetal-type tumoral hepatocytes and was associated with E-cadherin expression. Moreover, we show that beta-catenin is aberrantly overexpressed in a large spectrum of tumor components, including hepatocyte-like cells at various differentiation stages and heterologous elements such as squamous, osteoid and chrondroid tissues, and in occasional other mesenchymally-derived cells. These data strongly suggest that activation of beta-catenin signaling is an obligatory step in HB pathogenesis, and raise the possibility that it interferes with developmental signals that specify different tissue types at early stages of hepatic differentiation.

Bioactivity of sol-gel bioactive glass coated alumina implants.

Alumina on alumina total hip arthroplasty has been in use for more than 25 years with encouraging results. However, an improvement of the alumina/bone interface still is required. The objective of this study was to investigate the in vitro and in vivo osteoconductive properties of sol-gel bioactive glass coated alumina implants. Two sol-gel glass compositions (58S Bioglass(R) and 77S Bioglass(R)) were used as coatings on alumina substrates and implanted in a rabbit model. The 58S sol-gel coating was employed in two configurations, single (A58S1) and double layer (A58S2). SEM analysis after one week in simulated body fluid revealed small crystals assumed to represent the initial phase of hydroxyapatite formation, whereas no clear conclusion could be drawn from Fourier transform infrared spectroscopy data. The percentage of bone in direct contact was greater for coated implants when compared to bulk alumina implants (p <0.001). In the case of A58S1 implants, bone percentage significantly increased from 45.1% after 3 weeks up to 87. 8% after 24 weeks of implantation (p = 0.0004). The presence of osteoid tissue, related to an aluminum release from the alumina substrates, was greatly diminished when compared to melt-derived glass-coated alumina implants.

Biocompatibility of the polyurethane resin of the castor bean inserted into the alveolar bone of the dog

The biocompability of the polyurethane resin of the castor bean (Ricinus vulgaris) was studied following its insertion into the alveolar bone of dogs, after extraction of their premolar teeth. The resin was left to polymerise in the dental alveolus. Excess of material due to polymerisation was removed and polishing was employed to smooth and adapt the occlusal surface to the margins of the alveolar bone. This allowed a perfect suture of the mucosa together with the periosteum. The resin remained in the dental alveolus for 90 days. It was observed that the polyurethane was replaced by osteoid and bone tissues and no immune or inflammatory reactions were detected. There has been work on and discussion about the use of the polyurethane in grafts, prostheses and orthoses. Attention was paid to all the surgical steps, in particular the preservation of the periosteal integrity. Further research is being followed in our Department in order to test the biocompatibility of the material presented in this paper when used together with metallic or ceramic implants.

Biology of the calcium phosphate integration in human long bones

Calcium phosphate ceramics implanted in bones are integrated following a sequence of biological events which has already been described. We had the opportunity to analyze histologically some HA-ceramic samples that had been implanted in humans for various periods of time. Eight biopsies were obtained from calcium phosphate ceramics implanted in different sites. All the samples were implanted for periods ranging from 4 to 15 months. The samples were fixed in ethanol and embedded in hydroxyethylmetacrylate or polymethyl methacrylate. 5 μm thick sections were prepared and stained with Giemsa or by Von Kossa method. Alkaline phosphatase and tartrate resistant acid phosphatase (TRAP) were revealed by histochemical methods. Different osteointegration stages were evidenced. In early stages, hematoma remnants were still visible. These implants were invaded by a loose connective tissue in which some cell condensations were apparent. They lead to the formation of bone trabeculae by direct ossification. Some osteoblasts differentiated at the ceramic surface and synthesized osteoid tissue on the material. The fibroblast-like cells of the loose connective tissue were TRAP+. Most of them had TRAP+ nucleus and contained no cytoplasm vesicles. Multinucleated TRAP+ osteoclasts showing TRAP- negative nuclei were found in Howship's lacunae at the bone surface. Certain implants were integrated within mature bone in a later stage.

Volume effect on biological properties of a calcium phosphate hydraulic cement: experimental study in sheep

Injectable calcium phosphate hydraulic cements (CPHC) are a new family of bone substitutes within the class of bone reconstruction biomaterials. In this work, CPHC were tested in two consistencies (preset blocks or liquid paste) in an experimental model of cancellous bone defect in sheep. The defects were eight times larger than those investigated previously in rabbits. Three delays (12, 24, and 52 weeks) were used. Before death, a double label of oxytetracycline and alizarine was made intravenously. The distribution of implants was randomized, histomorphometric evaluation was performed and compared with micrographic observation, and optical microscopy of stained sections was performed either under visible, ultraviolet, or polarized light. The results were compared with spontaneous healing of empty defects and with a control group of normal cancellous bone from sheeps of the same age. No significant difference has been observed between premolded and injected implants. In the sheep model, the degradation and new bone formation rates are three times slower, compared with those observed previously in rabbits. New bone formation increased from 5.9% (12 weeks) up to 11.0% (24 weeks) in the empty defect group. In the cement groups, 28.3% new bone was obtained at 12 weeks, which seemed then to level off (27.8% new bone at 24 weeks). Cement residues appear as radio-opaque cylinders on microradiographs. In all cases, a radiolucent layer was observed at the cement/bone interface at 24 weeks. Stained sections showed the formation of a fibroconnective capsule around the residual cement, which presumably slows down new bone formation. Nevertheless, quantitative bone remodeling was accelerated in the cement group; mineral apposition as well as adjusted apposition rates were higher, and the formation period as well as the mineralization of osteoid tissue were faster compared with empty cavities and controls. These results point to higher osteoblast activity and better exchange with surrounding tissues in the defects filled with cement.

Maxillary ossification in a series of six human embryos and fetuses aged from 9 to 12 weeks of amenorrhea: clinical implications.

An anatomic controversy exists concerning the number of nuclei of ossification of the maxilla in human embryos and fetuses. Many authors have described two maxillary ossification nuclei, an incisor nucleus and a maxillary nucleus properly so-called. Some of these have explained congenital labiomaxillary clefts by a defect of bony fusion between these two ossification nuclei. Others consider that there is only a single nucleus for maxillary ossification. In order to settle this question we performed a histologic study in six heads of embryos and fetuses aged from 9 to 12 weeks of amenorrhea (WA) to demonstrate the presence of one or more sites of maxillary ossification at the earliest stages. Our study revealed, on each side, a single zone of maxillary ossification, present from 9 WA, in the form of a sheet of osteoid tissue situated in close contact with the dental lamina. Maxillary ossification then progressed in the lateromedial direction, preserving a median transverse and ventral mesenchymal septum. This septum may constitute the phylogenetic remnant of an ancestral premaxilla.

Osteopontin. Between a rock and a hard plaque.

Vascular calcification is widely regarded as merely a rare, end-stage, passive, degenerative, and inevitable process of aging. Decades ago, atherosclerosis had been similarly dismissed, but extensive research finally demonstrated its active regulation. Current research is now revising outdated views of vascular calcification. New imaging techniques made it clear that coronary calcification is neither rare nor end stage but occurs in 90% of patients with coronary artery disease1 and that the vast majority of significant coronary stenoses are calcified.2 Coronary calcification is also associated with increased cardiovascular risk.3 4 One clue to the regenerative—rather than degenerative—nature of vascular calcification is that it often includes histopathological features of bone. In the 1700s, Morgagni and others described arterial ossification in their postmortem examinations: “… the left coronary artery appeared to have been changed into a bony canal from its very origin… . ”5 In 1863, Virchow labeled the vascular changes as “ossification, not mere calcification, occurring by the same mechanism by which an osteophyte forms on the surface of bone.”6 In 1906, marrow was described within the bone tissue within the arteries—a richly vascularized cellular red marrow containing adipocytes, neutrophils, eosinophils, lymphoid and erythroid cells, reticulocytes, megakaryocytes, and other characteristic elements of marrow.7 Bunting further described (and we have also observed) evidence of resorption by osteoclast-like cells in this tissue. Within the vascular tree, the aorta and cardiac valves are the most common sites of ossification, and these contain all the stages of osteogenesis from the youngest variety of osteoid tissue up to true bone.8 Calcification of cardiac valves also involves lipid deposition and expression of bone matrix proteins.9 Because of various selection bias effects, the ossified …

Giant cell tumor of bone in an aged Fischer 344 rat.

A giant cell tumor (GCT) was detected on the distal end of the femur in a 98-wk-old male Fischer 344 rat. The yellowish white mass had expanded, compressing adjacent muscle tissues. The tumor had an osteolytic and relatively homogeneous appearance and was composed of multinuclear giant cells scattered in a mass of mononuclear stromal cells. No osteoid tissue formation was observed. The tumor cells were strongly immunoreactive for ED-1 and some were also positive for alpha-smooth muscle actin, suggesting that the tumor originated from the monocyte/macrophage lineage showing myofibroblastic differentiation. This is the first report concerning spontaneous GCT of bone in a rat.