Osteoid Tissue Research Articles

PS-094 The Levels Of Bone Alkaline Phosphatase And Human Epidermal Growth Factor Receptor-2 In Patients With Osteosarcoma

Background and aims Osteosarcoma (OS) is a primary malignant bone tumour, deriving from primitive bone-forming mesenchyme and characterised by the production of osteoid tissue or immature bone. The importance of bone alkaline phosphatase (BALP) and human epidermal growth factor receptor-2 (HER-2) as prognostic markers is still discussed. The aim of this study was to investigate serum levels of BALP and HER-2 in patients with OS during clinical treatment. Methods We studied 22 patients (5 girls, 17 boys) at the age 7–20 years with osteosarcoma treated at the Institute of Mother and Child in Warsaw. All patients were evaluated for the serum levels of BALP and HER-2 before treatment onset, during pre- and postoperative chemotherapy and after termination of treatment. Healthy children (n = 22) were the reference group. The levels of BALP and HER-2 were measured using immunoenzymatic methods. Results The values of BALP and HER-2 proteins were higher (p Conclusions Our results demonstrate different pattern of BALP and HER-2 proteins during clinical treatment. However, low values of both markers during therapy may characterise remission of disease and favourable prognosis for patients with OS. Further longitudinal studies are necessary to confirm the prognostic values of BALP and HER-2 proteins in this group of patients.

Fiber-enriched calcium phosphate cement implanted in the femur of rats: a histological evaluation.

We performed a histological analysis of nylon, carbon, and polypropylene fiber-enriched calcium phosphate cement (CPC) for use as bone substitute in the femur or rats. Fiber-enriched CPC blocks (6-mm diameter, 2-mm thickness) were implanted in the femur of 20 male Wistar rats. The animals were euthanized at 30, 60, 90, and 120 days, with removal and histological evaluation of the specimens. Biocompatibility, resorption and osteoconduction were evaluated. At all time points, histological analysis revealed the formation of dense connective tissue with low cellularity, little vascularization and a few mononuclear cells. Surrounding the implant, slight resorption and hyalinization of peripheral collagen fibers were observed, with evidence of incorporation of implant material into connective tissue. Osteoid tissue was observed at 120 days. Bone resorption surrounding the implant was not significant. Based on the present criteria, CPC seems adequate for use as a bone substitute. Keywords: Biomaterials. Bone substitutes. Calcium Phosphate Cements.

Ectopic osteoid and bone formation by three calcium-phosphate ceramics in rats, rabbits and dogs.

Calcium phosphate ceramics with specific physicochemical properties have been shown to induce de novo bone formation upon ectopic implantation in a number of animal models. In this study we explored the influence of physicochemical properties as well as the animal species on material-induced ectopic bone formation. Three bioceramics were used for the study: phase-pure hydroxyapatite (HA) sintered at 1200°C and two biphasic calcium phosphate (BCP) ceramics, consisting of 60 wt.% HA and 40 wt.% TCP (β-Tricalcium phosphate), sintered at either 1100°C or 1200°C. 108 samples of each ceramic were intramuscularly implanted in dogs, rabbits, and rats for 6, 12, and 24 weeks respectively. Histological and histomorphometrical analyses illustrated that ectopic bone and/or osteoid tissue formation was most pronounced in BCP sintered at 1100°C and most limited in HA, independent of the animal model. Concerning the effect of animal species, ectopic bone formation reproducibly occurred in dogs, while in rabbits and rats, new tissue formation was mainly limited to osteoid. The results of this study confirmed that the incidence and the extent of material-induced bone formation are related to both the physicochemical properties of calcium phosphate ceramics and the animal model.

Primary aneurysmal bone cyst of the distal tibial epiphysis

Aneurysmal bone cyst (ABC) is a benign lesion that commonly involves the metaphysis or metadiaphyseal region of long bones in children. The WHO defined ABC as an expansile osteolytic lesion consisting of blood-filled spaces and channels that are divided by connective tissue septa that may contain osteoid tissue and osteoclast-like giant cells. ABCs are usually treated with intralesional procedures, and variables including surgeon technique, young patient, juxtaphyseal tumors, and tumor location have been associated with recurrence. Juxtaphyseal lesions breaching the physis have been described. There is only one case of primary ABC of the epiphysis in the literature. We present a second case in a 13-year-old boy who presented with a primary ABC of the distal tibial epiphysis, including diagnostic evaluation and treatment.

A rare case of an aggressive osteoblastoma of the squamous temporal bone: A unique presentation with literature review

Aggressive osteoblastoma is a rare osteoid tissue forming tumour commonly affecting the spine with predilection for the posterior elements. Calvarial involvement is extremely rare with only two reported cases in the literature. Due to its overlapping clinical, radiographic and histological features with ossifying fibroma, benign osteoblastoma and osteosarcoma, it is very difficult accurately to diagnose this lesion at an early stage. A rare case of an aggressive osteoblastoma of the squamous temporal bone in a young male is presented here which was misdiagnosed twice before reaching the final diagnosis by correlating clinical, radiographic and histopathological features.

Intra-articular Osteoid Osteoma of the Proximal Ulna

Osteoid osteoma is a common benign osteogenic bone neoplasm characterized histologically by increased osteoid tissue formation with an intracortical nidus surrounded by cortical thickening and vascular fibrous stroma and sclerosis. The clinical presentation classically includes severe nocturnal pain that is improved with nonsteroidal anti-inflammatory drugs. Younger men (second and third decades) have the highest incidence, with the most frequent sites of involvement being the long bones or axial skeleton. Osteoid osteoma may be missed due to the lesion occurring in an atypical location or due to failure to obtain advanced imaging studies such as computed tomography (CT). Intralesional or wide excision, or CT-guided radiofrequency ablation if available, leads to predictable and rapid pain relief. The authors report the case of a 24-year-old man who had a painful flexion contracture of his dominant right elbow for 1.5 years, secondary to an intra-articular osteoid osteoma. Attempted motion, passive or active, produced a marked exacerbation of pain. Previous surgeries, including an elbow synovectomy and an ulnar nerve transposition, had been unsuccessful in relieving his pain. Plain radiographs demonstrated a small area of periosteal thickening adjacent to the sublime tubercle. Fine-cut CT scan demonstrated an osteoid osteoma within the articular surface of the trochlear notch of the olecranon, adjacent to the sublime tubercle. Because of a perceived risk to the surrounding articular cartilage, CT-guided radiofrequency ablation was not performed. Wide en bloc surgical excision of the nidus was performed, with complete resolution of pain and rapid return to normal function.

Ovarian tumours in Arabian mares

Of 222 infertile Arabian mares, unilateral ovarian enlargement was detected in three cases. Ultrasonography suggested the presence of ovarian tumours. Blood samples were taken for hormonal analysis, and the mares underwent surgery for ovarian exploration. Ovarian specimens were processed for microscopic examination. On histopathology, an adult-type granulosa cell tumour (GCT), a mixed germ cell tumour and a low-grade Sertoli cell tumour were diagnosed. The GCT (6.5 cm in diameter) was rounded and cystic, with a central hypoechogenic area. The ovarian tissue was entirely replaced by polygonal neoplastic cells. The mixed germ cell tumour (15.3 cm in diameter) was hard and non-homogeneous. The ovary contained insular patterns of round, oval or spindle cells with myxomatous and hyalinised stroma. The stroma also contained osteoid tissue. The ovarian low-grade Sertoli cell tumour (19 × 20 cm) was a solid, fairly round homogeneously echogenic structure. The ovarian tissue was completely replaced by aggregated tubules lined by Sertoli-type cells surrounded by abundant fibrous stroma. The three types of tumours secreted relatively low levels of estradiol 17β and progesterone, whereas the level of inhibin-B was extremely high in the case of the Sertoli cell tumour. In conclusion, this study described three types of ovarian tumours causing infertility in Arabian mares. Furthermore, the Sertoli cell tumour is described here for the first time in mares.

Aneurysmal bone cyst of the mandible: Report of a case with a review of the literature

Aneurysmal bone cyst (ABC), is a rare benign osteolytic bone neoplasm of bone tissue characterized by several sponge-like blood or serum filled, generally non-endothelialized spaces of various diameters that can contain osteoid tissue and osteoclast-like giant cells. In this article, we describe a case of ABC in the mandibular corpus region with clinical, radiological and pathological findings and review the literature concerning the case. A 23-year-old male patient attended to our clinic with the complaint of a mild-pain on the left posterior lower jaw since two months. The superior margin of the lesion was extending between the apical third parts of the roots of the teeth 35-38. Cone beam computed tomography (CBCT) was performed. CBCT Slices revealed an expansile lesion with hydraulic-appearing outer margins above the mandibular canal. Excisional surgical treatment was performed after raising a mucoperiosteal flap and finalized with curette of lesion under local anesthesia. Diagnosis of aneurysmal bone cyst was confirmed by histopathological evaluation. The patient was pain free after six months follow-up, and panoramic radiography showed no evidence of recurrence. The ABC is most common in those regions of the skeleton where there is a relatively high venous pressure and high marrow content. Clinical presentation of the ABC varies from a small, indolent, asymptomatic lesion to rapidly growing, expansile, destructive lesion causing pain, swelling, deformity, neurologic symptoms, pathologic fracture, and perforation of the cortex. As the radiologic and clinical presentation of ABC is extremely variable, histopathologic examination is placed a great emphasis on for the diagnosis.

Long-term observation of osteomalacia caused by adefovir-induced Fanconi's syndrome.

A 64-year-old man suffering polyarthralgia and bone pain was referred to our hospital. Renal dysfunction, hypophosphatemia and increased levels of bone alkaline phosphatase were found. The patient's serum creatinine level had gradually increased after the initiation of adefovir dipivoxil administration for hepatitis B. In agreement with multifocal uptakes of bone scintigraphy, iliac bone biopsy revealed an abnormal increase in osteoid tissues. Reducing the dose of adefovir and initiating the administration of eldecalcitol were effective for reducing proteinuria and glucosuria, and for ameliorating bone pain with an increase in serum phosphate level. This case first showed a clinical course of hypophosphatemic osteomalacia caused by secondary Fanconi's syndrome for 8 years after adefovir administration. Early diagnosis is important for the reversibility of bone damage and for a better renal prognosis.

Scanning Electron Microscopy Observations of Osseointegration Failures of Dental Implants that Support Mandibular Overdentures

: Investigating possible failure causes of mandibular implants after their immediate loading with an overdenture retained with bilateral bar attachments, using scanning electron microscope. Twenty edentulous male patients were included in the present study. Each patient had 2 fixtures inserted in the canine and the first molar areas on each side of the mandible. After abutments screwing, the 2 fixtures on the same side were splinted with a bar, and immediately loaded with an overdenture. Implants mobility was assessed on weekly basis. Failed implants were removed, and examined by scanning electron microscope. The failed implants, removed after 4 weeks of treatment, showed an intimate contact of mineralized and osteoid tissues with dense collagen-rich matrix in the apical third of implants. Furthermore, newly developed bone was observed at the same area in implants removed after 7 weeks. However, there was no evidence of such growth at the middle and/or cervical thirds in either case. Lack of osseointegration at the middle and cervical thirds of the root could be a possible cause of implant failure. Early loading by an overdenture retained with bilateral bars is considered a major contributing factor to incomplete osseointegration of the supporting implants.

Advanced glycation end products suppress lysyl oxidase and induce bone collagen degradation in a rat model of renal osteodystrophy

Renal osteodystrophy (ROD) is a major problem in patients with renal insufficiency. The present study was designed to elucidate the role of bone collagen changes and osteoblast differentiation in a rat model of ROD pathogenesis induced by adenine. Typical characteristics of renal failure, including increased serum urea nitrogen, creatinine, inorganic phosphorus, and intact parathyroid hormone levels, and decreased serum calcium and 1,25(OH)2D3 levels, were observed in adenine-induced rats. Micro-computed tomography analysis of the femur in adenine-induced rats showed decreased bone mineral density and osteoporotic changes, confirmed by the three-point bending test. The cancellous bone histomorphometric parameters of the tibia showed increased osteoblast number, decreased osteoclast surface with peritrabecular fibrosis, and increased osteoid tissue, indicating a severe mineralization disorder similar to clinical ROD. Scanning and transmission electron microscopy revealed irregular alignment and increased diameter of bone collagen fibrils in adenine-induced rats. Protein expression analysis showed greater accumulation of advanced glycation end products (AGEs) in peritrabecular osteoblasts of adenine-induced rats than in the controls. In contrast, suppressed expression of runt-related transcription factor 2, alkaline phosphatase, secreted phosphoprotein 1 (Spp1), and lysyl oxidase (Lox) mRNA levels, particularly the amount of active LOX protein, were observed. In in-vitro experiments, mineralizing MC3T3-E1 osteoblastic cells stimulated with AGE-modified bovine serum albumin had attenuated the expression of Spp1 mRNA levels and active LOX protein, with a decrease in extracellular nodules of mineralization. These observations provide clues to ROD pathogenesis, as they indicate that the suppression of osteoblast differentiation and decreased active LOX protein associated with accumulation of AGEs in osteoblasts caused structural abnormalities of bone collagen fibrils and a severe mineralization disorder, leading to bone fragility.

Immature muscular tissue differentiation into bone‐like tissue by bone morphogenetic proteins in vitro, with ossification potential in vivo

The objective of this study was to induce bone formation from immature muscular tissue (IMT) in vitro, using bone morphogenetic proteins (BMPs) as a cytokine source and an expanded polytetrafluoroethylene (ePTFE) scaffold. In addition, cultured IMTs were implanted subcutaneously into Sprague-Dawley (SD) rats to determine their in vivo ossification potential. BMPs, extracted from bovine cortical bones, were applied to embryonic SD rat IMT cultures, before 2 weeks culture on ePTFE scaffolds. Osteoblast-like cells and osteoid tissues were partially identified by hematoxylin-eosin staining 2 weeks after culture. Collagen type I (Col-I), osteopontin (OP), and osteocalcin (OC) were detected in the osteoid tissues by immunohistochemical staining. OC gene expression remained low, but OP and Col-I were upregulated during the culture period. In vivo implanted IMTs showed slight radiopacity 1 week after implantation and strong radiopacity 2 and 3 weeks after implantation. One week after implantation, migration of numerous capillaries was observed and ossification was detected after 2 weeks by histological observation. These results suggest that IMTs are able to differentiate into bone-like tissue in vitro, with an ossification potential after implantation in vivo.

Enhanced Healing of Rat Calvarial Critical Size Defect with Selenium-Doped Lamellar Biocomposites

A 3D porous lamellar selenium-containing nano-hydroxyapatite (SeHAN)/chitosan (CS) biocomposite was synthesized. The selenium-containing hydroxyapatite (HA) grains of 150~200 nm in length and 20~30 nm in width were observed by dynamic light scattering and transmission electron microscopy. A combination of X-ray diffraction, Fourier-transform infrared spectroscopy, and SEM indicated that HA particles were uniformly dispersed in chitosan matrix and there was a chemical interaction between chitosan and HA. Then, a standard critical size calvarial bone defect was created in Wistar rats. In group 1, no implant was made in the defect. In groups 2 and 3, HA nanoparticles (HAN)/CS biocomposite and SeHAN/CS biocomposite were implanted into the defect, respectively. After 4 weeks, the histological assessment clearly exhibited no significant changes, only found some living cells anchored in the periphery of the implants. After 8 and 12 weeks, most newly formed osteoid tissue was found in the SeHAN/CS implant group. Additionally, the newly formed osteoid tissue, both at the edge and in the center of implants, was bioactive and neovascularized. Microfocus computerized tomography measurements also confirmed the much better quality of the newly formed bone tissue in SeHAN/CS implant group than that in HAN/CS implant group (p < 0.01). Collectively, the SeHAN/CS biocomposite, as a bioactive bone grafting substitute, significantly enhanced the repair of bone defect.

Bone Repair is Influenced by Different Particle Sizes of Anorganic Bovine Bone Matrix

The aim of this study was to analyze histologically and radiographically the influence of particle size of anorganic bovine bone matrix (ABBM) on bone repair. Four calvarial defects of 8 mm each were prepared in 18 adult New Zealand rabbits. The defects were then filled with either particulate autogenous bone (control group) or ABBM of large, medium, and small size granules. The animals were sacrificed at 15, 30, and 60 days after surgery. The samples were radiographically examined before being submitted to histological processing. Autogenous bone showed a slight radiopacity at the beginning, which was increased at the final period, being very similar to the adjacent bone tissue. The large and medium size ABBM particles maintained the same radiographic behavior, showing a radiolucent area in the central portion of the defect at 60 days. ABBM of small size granules showed a slight radiolucity at the initial period, which was increased at the subsequent periods. More intense bone formation occurred in the control group (autogenous bone). All 3 particle sizes of the biomaterial resulted in inflammatory infiltration at 15 and 30 days. ABBM of small size granules lead to a greater amount of osteoid tissue, and the particles were almost totally reabsorbed within 60 days of implantation. Autogenous bone graft lead to the best result in terms of bone defect repair; ABBM of large and medium size granules are not totally reabsorbed at the observed period; ABBM of small size granules was more intensively reabsorbed and led to a greater osteoid tissue formation when compared to the medium and large ABBM granules.

External cervical resorption: an analysis using cone beam and microfocus computed tomography and scanning electron microscopy

To provide a three-dimensional representation of external cervical resorption (ECR) with microscopy, stereo microscopy, cone beam computed tomography (CT), microfocus CT and scanning electron microscopy (SEM). External cervical resorption is an aggressive form of root resorption, leading to a loss of dental hard tissues. This is due to clastic action, activated by a damage of the covering cementum and stimulated probably by infection. Clinically, it is a challenging situation as it is characterized by a late symptomatology. This is due to the pericanalar protection from a resorption-resistant sheet, composed of pre-dentine and surrounding dentine. The clastic activity is often associated with an attempt to repair, seen by the formation of osteoid tissue. Cone beam CT is extremely useful in the diagnoses and treatment planning of ECR. SEM analyses provide a better insight into the activity of osteoclasts. The root canal is surrounded by a layer of dentine that is resistant to resorption.

An unusual location of osteolipoma: a case report

Lipomas are the most common benign tumors of soft tissue in adults [1]. They may be located in either deep or surface tissues. Deep tissue-located lipomas are classified as intramuscular, intermuscular, parosteal, and interosseous lipomas [1]. It is common to encounter intraosseous lipomas originating from bony tissues, whereas it is very rare to encounter adipocytic cells with osteoid and/or chondroid tissues independent of bony tissues [2]. Osteoid lipomas (benign osteoid lipoma, osteolipoma, degenerative osteolipoma) are lipomas containing mature osteoid tissues [3, 4]. Osteoid lipomas are reported to be less than 1 % in the literature [2]. Osteolipomas, which found independent of bony tissue, are rare kind of tumors [5]. In our study, we intend to report a rare case of osteolipoma with a rare location independent of bony tissue and to emphasize that this lesion should be included in differential diagnosis of lipomatous lesions present in extremities.

Sclerosing rhabdomyosarcoma presenting in the masseter muscle: a case report

Sclerosing rhabdomyosarcoma (SRMS) is exceedingly rare, and may cause a great diagnostic confusion. Histologically, it is characterized by abundant extracellular hyalinized matrix mimicking primitive chondroid or osteoid tissue. So, it may be easily misdiagnosed as chondrosarcoma, osteosarcoma, angiosarcoma and so on. Herein, we report a case of SRMS occurring in the masseter muscle in a 40-year-old male. The tumor showed a diverse histological pattern. The tumor cells were arranged into nests, cords, pseudovascular, adenoid, microalveoli and even single-file arrays. Immunostaining showed that the tumor was positive for the Vimentin, Desmin and MyoD1, and was negative for CK, P63, NSE, CD45, CD30, S-100, CD99, Myoglobin, CD68, CD34, CD31, and α–SMA. Based on the morphological finding and immunostaining, it was diagnosed as a SRMS. In addition, focally, our case also displayed a cribriform pattern resembling adenoid cystic carcinoma. This may represent a new histological feature which can broaden the histological spectrum of this tumor and also may lead to diagnostic confusion.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1615846455818924

A nano-hydroxyapatite – Pullulan/dextran polysaccharide composite macroporous material for bone tissue engineering

Research in bone tissue engineering is focused on the development of alternatives to allogenic and autologous bone grafts that can stimulate bone healing. Here, we present scaffolds composed of the natural hydrophilic polysaccharides pullulan and dextran, supplemented or not with nanocrystalline hydroxyapatite particles (nHA). In vitro studies revealed that these matrices induced the formation of multicellular aggregates and expression of early and late bone specific markers with human bone marrow stromal cells in medium deprived of osteoinductive factors. In absence of any seeded cells, heterotopic implantation in mice and goat, revealed that only the composite macroporous scaffold (Matrix + nHA) (i) retained subcutaneously local growth factors, including Bone Morphogenetic Protein 2 (BMP2) and VEGF165, (ii) induced the deposition of a biological apatite layer, (iii) favored the formation of a dense mineralized tissue subcutaneously in mice, as well osteoid tissue after intramuscular implantation in goat. The composite scaffold was thereafter implanted in orthotopic preclinical models of critical size defects, in small and large animals, in three different bony sites, i.e. the femoral condyle of rat, a transversal mandibular defect and a tibial osteotomy in goat. The Matrix + nHA induced a highly mineralized tissue in the three models whatever the site of implantation, as well as osteoid tissue and bone tissue regeneration in direct contact to the matrix. We therefore propose this composite matrix as a material for stimulating bone cell differentiation of host mesenchymal stem cells and bone formation for orthopedic and maxillofacial surgical applications.

Repair of critical-sized bone defects of the femoral condyle with nano-hydroxyapatite/chitosan composites in rabbits

Objective To investigate the bone regeneration potential of nano-hydroxyapatite/chitosan composite scaffolds when implanted into critical-sized bone defects in rabbit femoral condyles.Methods Critical-sized bone defects (6 mm in diameter and 10 mm in depth) were created in the left femoral condyles of 44 adult New Zealand white rabbits.All the rabbits were randomly divided into 3 groups according to bone grafts.Nano-hydroxyapatite/chitosan compositions were implanted into the defects in the experimental group (n =20),pure chitosan in the control group (n =20),and nothing in the blank group (n =4).New bone formation was detected and compared among the 3 groups by gross observation,plain radiography,quantitative computer tomography (CT) and histological examination at 8 and 12 weeks after surgery.Results Plain radiography at 12 weeks after surgery showed that bone defects were being repaired well and cortical bone union was observed in the experimental group,and that the depth of defect diminished but bony connection was not achieved in the control group,and that there was no new bone formation in the blank group.The Lane-Sandhu X-ray scores were 10.18 ±0.98 in the experimental group and 8.90 ±0.99 in the control group,with a significant difference between the 2 groups (t =6.858,P =0.000).At 12 weeks,CT showed that the defects were almost filled with new osteoid tissue and the bone contour remodeled smoothly in the experimental group; most of the defects were filled with new osteoid tissue but still visible in the control group; bony union was not achieved and the defects were still very obvious in the blank group.The CT scores were 256.1 ± 26.8 Hu in the experimental group and 169.2 ± 25.4 Hu in the control group,with a significant difference (t =4.711,P =0.003).The histological observation showed a lot of trabecular bone in the bone defects at 12 weeks in the experimental group,with no visible boundary between newly formed bone tissue and native bone.In the control group,the bone defects were full of the remnant material and fibrous tissue at 12 weeks.In the blank group,the bone defects were filled with a little fibrous tissue at 12 weeks but no new bone formed.Conclusion Since nano-hydroxyapatite/chitosan composite scaffolds may have better performance than pure chitosan in repair of bone defects,it is a sort of promising candidate material for regeneration of bone loss. Key words: Femur; Hydroxyapatites; Chitosan; Nano-composites; Bone defect

Osteoid osteomas: a pain in the night diagnosis

Osteoid osteoma is a common benign bone-forming lesion that is composed of a nidus of vascular osteoid tissue and woven bone lined by osteoblasts. It is frequently associated with considerable surrounding inflammation. The diagnosis is usually straightforward when imaging reveals a radiolucent nidus surrounded by variable degrees of reactive sclerosis. However, the diagnosis can be elusive when osteoid osteomas occur in atypical locations, as they may have a nonspecific and misleading appearance on different imaging modalities, particularly on MRI. The purpose of this pictorial essay is to review the typical and atypical features of osteoid osteomas on different imaging modalities, and the appearance of osteoid osteomas in different locations. We also review growth disturbances caused by osteoid osteomas and potential mimickers, with imaging characteristics that can aid in diagnosis.