Osteoid Formation Research Articles

Pathology Quiz Case 1

A N 89-YEAR-OLD MAN PRESENTED WITH A LEsion on the left temple. For the past several years, the patient had experienced multiple benign actinic lesions of his face and scalp that would slough off. The left temple lesion concerned the patient because over the previous 4 months, it had bled intermittently. He denied a history of radiation or trauma to the area. The patient admitted to a 1-year history of anorexia, increasing fatigue, and exertional dyspnea but denied any bony abnormalities or pain. His medical history was significant for bilateral carotid stenosis, diabetes mellitus, psoriasis, chronic renal failure, and eczema. Physical examination revealed a flat, violaceous cutaneous lesion measuring 2 2 cm with a 1 1-cm central ulceration on the left temple. The lesion was mobile, with no fixation to subcutaneous tissues, and there were no obvious bony deformities. There was no palpable adenopathy. The patient’s chronic renal failure precluded contrast-enhanced axial imaging. A positron emission tomographic scan with a computed tomographic study did not reveal any other areas of fluorodeoxyglucose F 18 avidity. Given the indeterminate length of time that the patient had the lesion with associated ulceration, a biopsy was performed, which showed dermal infiltrating sheets of high-grade pleomorphic cells admixed with benign and malignant, osteoclast-type, multinucleated giant cells. Osteoid formation was visualized in a fine, ramifying, lacelike, and coarse trabecular pattern (arrowheads in Figure 1). Atypical mitotic figures were also prominent (arrow, Figure 2). Immunohis tochemica l ana lyses were negat ive for pancytokeratin, panmelanoma, and epithelial membrane antigen (EMA). What is your diagnosis?

Primary osteosarcoma of the thyroid gland: report of a rare neoplasm

Primary mesenchymal tumors of the thyroid gland are extremely rare. The authors report a case of primary thyroid osteosarcoma in a male patient presenting a tumoral mass in the neck. CT scan demonstrated a large tumor in the right thyroid lobe with areas of calcification. The surgical specimen consisted of a hard brown-gray tumor, measuring 13 × 11 × 7.5 cm. Microscopy revealed a high-grade malignant neoplasm composed of polygonal cells of intermediate size, chondroid pattern in some areas and osteoid formation. The process was immunonegative for AE1/AE3, glial fibrillary acidic protein (GFAP), epithelial membrane antigen (EMA), p53 and thyroid transcription factor-1 (TTF-1), and immunopositive for CD99 and S100. Thus the diagnosis of primary osteosarcoma of the thyroid gland was established.

A Case of Rapidly Growing Osteosarcoma of the Rib

A 37-year-old woman noticed a right anterior chest mass and pain. The mass had been rapidly growing and she visited our hospital. The mass was hard and 8 × 7 cm in size. It was detected in the upper inner quadrant of her anterior chest wall. A computed tomography (CT) examination and magnetic resonance imaging (MRI) of the chest revealed a large heterogeneously enhanced mass arising from the right chest wall with lytic destruction of the rib and coarse calcification. An image diagnosis of osteogenic sarcoma originating from a rib was made. She underwent surgical excision of the tumor and chest wall reconstruction. Microscopic examination of the resected tumor showed multiple neoplastic cells accompanied by osteoid formation within the tumor. The tumor was diagnosed as high-grade malignant osteosarcoma of the rib. Primary osteosarcoma commonly originates in the long bone in children and adolescents, but it occurs very rarely in the ribs in adults. Surgical resection plays an important role in the treatment for this disease. We report a case of primary osteosarcoma that originated in the rib of a young woman and was treated successfully by surgery.

Peripheral Primitive Neuroectodermal Tumor with Osseous Component of the Small Bowel Mesentery: A Case Study

A case of peripheral primitive neuroectodermal tumor of the small bowel mesentery with osseous component is reported. A 23-year-old man was admitted to our hospital because of acute severe abdominal pain. Abdominal computed tomography revealed a large solid and cystic, oval shaped mass, measuring 11.0×6.0 cm in the pelvic cavity. Histologically the resected lesion consisted of sheets of undifferentiated small round cells forming Homer-Wright rosettes and perivascular pseudorosettes, and showed areas of osteoid and bone formation. Immunohistochemical studies revealed that tumor cells expressed positivity against CD99 (MIC2), CD57, neuron-specific enolase, and vimentin. Fluorescence in situ hybridization study revealed Ewing sarcoma breakpoint region 1 (EWSR1) gene rearrangement on chromosome 22q12. To the authors' knowledge this is the first documentation of a peripheral neuroectodermal tumor with osteoid and bone formation of the small bowel mesentery.

3D printed tricalcium phosphate scaffolds: Effect of SrO and MgO doping on in vivo osteogenesis in a rat distal femoral defect model.

The presence of interconnected macro pores is important in tissue engineering scaffolds for guided tissue regeneration. This study reports in vivo biological performance of interconnected macro porous tricalcium phosphate (TCP) scaffolds due to the addition of SrO and MgO as dopants in TCP. We have used direct three dimensional printing (3DP) technology for scaffold fabrication followed by microwave sintering. Mechanical strength was evaluated by scaffolds with 500 µm, 750 µm, and 1000 µm interconnected designed pore sizes. Maximum compressive strength of 12.01 ± 1.56 MPa was achieved for 500 µm interconnected designed pore size Sr-Mg doped scaffold. In vivo biological performance of the microwave sintered pure TCP and Sr-Mg doped TCP scaffolds was assessed by implanting 350 µm designed interconnected macro porous scaffolds in rat distal femoral defect. Sintered pore size of these 3D printed scaffolds were 311 ± 5.9 µm and 245 ± 7.5 µm for pure and SrO-MgO doped TCP scaffolds, respectively. These 3D printed scaffolds possessed multiscale porosity, i.e., 3D interconnected designed macro pores along with intrinsic micro pores. Histomorphology and histomorphometric analysis revealed a significant increase in osteoid like new bone formation, and accelerated mineralization inside SrO and MgO doped 3D printed TCP scaffolds as compared to pure TCP scaffolds. An increase in osteocalcin and type I collagen level was also observed in rat blood serum with SrO and MgO doped TCP scaffolds compared to pure TCP scaffolds. Our results show that these 3D printed SrO and MgO doped TCP scaffolds with multiscale porosity contributed to early healing through accelerated osteogenesis.

Histologic and histomorphometric assessment of eggshell-derived bone graft substitutes on bone healing in rats.

Objective: The objective of this study was to histologically and histomorphometrically evaluate the efficacy of the new formulations of eggshell-derived calcium carbonate in rats. Study Design: The study was conducted on 30 adult male rats. Four standardized and circular intrabony defects were created in the both maxilla and mandibula of each animal. Three different graft materials were prepared as follows: 1) Material A: Eggshell-derived calcium carbonate combined with carrageenan gel, 2) Material B: Eggshell-derived calcium carbonate combined with xanthan gum gel, and 3) Material C: Eggshell-derived calcium carbonate powder. The right mandibular defect sites were grafted with Material A in all animals, and defects on the left were grafted with Material B. Defects on the right side of maxilla were received Material C in all animals, and all left maxillary defects were remained untreated as controls. The animals were sacrificed either postoperatively on the 15th day, postoperatively on the 30th day or postoperatively on the 45th day. Histomorphometric measurements were made of the areas of newly formed bone, necrotic bone, fibrous tissue and residual graft material. Results: Material A exhibited the highest level of osteoid formation followed by Material B and Material C on the 45th day. In terms of osteoid formation, statistically significant differences were observed between graft materials and controls at 45th day compared to 15th and 30th day (p<0.05). Conclusions: Eggshell-derived graft substitutes in both gel and powder forms are biocompatible materials which may have the potential to enhance the new bone formation. Key words:Bone graft material, bone defects, eggshell, histopathological evaluation, rat.

The Poor Osteoinductive Capability of Human Acellular Bone Matrix

Demineralized bone matrix (DBM) has extensive clinical use for bone regeneration because of its osteoinductive and osteoconductive aptitude. It is suggested that the demineralization process in bone matrix preparation is influential in maintaining osteoinductivity; however, relevant investigations, especially into the osteoinductivity of acellular bone matrix, are not often performed. This study addressed the osteoinductive capability of human acellular cancellous bone matrix (ACBM) after subcutaneous implantation in a rat model. The growth and osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells (rBM-MSCs) seeded in this material were also studied. Without the demineralization process, the ACBM we obtained had an interconnected porous network and the micropores in the surface were clearly exposed. After the ACBM was subcutaneously implanted for 4 months, new osteoid formation was noted but not typical mature bone formation. rBM-MSCs grew well in the ACBM and kept a steady morphology after continuous culture for 28 days. However, no mineralized nodule formation was detected and the expression levels of genes encoding osteogenic markers were significantly decreased. These results demonstrated that human ACBM possess the structural features of native bone and poor osteoinductivity; nonetheless this material helped to preserve the undifferentiated phenotype of rBM-MSCs. Such insights may further broaden our understanding of the application of ACBM for bone regeneration and the creation of stem cell niches.

Relationship of β-Catenin and Postchemotherapy Histopathologic Changes With Overall Survival in Patients With Hepatoblastoma

Histopathologic spectrum and expression of β-catenin were analyzed in patients with hepatoblastoma, diagnosed over a period of 14 years. These were correlated with the survival outcome. The morphologic features subsequent to chemotherapy were also analyzed. Histomorphologic features were studied on paraffin-embedded sections. There were 24 cases with 15 fetal, 4 embryonal, 4 macrotrabecular, and 1 of small cell subtype. Follow-up was available in 20 cases (mean = 16.8 mo). β-catenin immunostaining performed by indirect immunoperoxidase method revealed 14 cases with nuclear and 10 cases with cytoplasmic positivity. Statistical analysis revealed no significant correlation between morphologic subtype and survival. Significant difference in survival was noted with respect to tumor stage, mitotic index, and β-catenin staining pattern. Cases with nuclear expression had a mean survival of 71.54 ± 8.1 months in comparison with 14.71 ± 6.5 months in cases with cytoplasmic expression. Besides osteoid and cartilage formation, interesting postchemotherapy findings were the presence of tumoral maturation, hepatocellular carcinoma-like areas, peliotic-like foci, and "glomeruloid clusters." Nuclear β-catenin expression is not a poor prognostic factor and this might be indicative of different genetic alterations in hepatoblastoma in the Indian subcontinent. There was no significant correlation between histologic subtype and osteoid differentiation with survival. The histopathologic changes observed were peliotic-like areas, tumoral maturation, hepatocellular carcinoma-like changes, and glomeruloid clusters besides the well-established features of osteoid differentiation after chemotherapy.

Primary juxtacortical myoepithelioma/mixed tumor of the bone: a report of 3 cases with clinicopathologic, immunohistochemical, ultrastructural, and molecular characterization

We describe the clinicopathological, immunohistochemical, and molecular features of 3 primary juxtacortical myoepithelioma/mixed tumor of bone. The patients were 2 males (13 and 23 years of age) and a 15-year-old female. The juxtacortical lesions were all located in the femur, and were surgically removed, 2 with wide margins and one with marginal margins. This latter tumor recurred locally 18 months later. The 3 patients were free of disease at 6 to 17 months follow-up. Histologically, all lesions showed a prominent multinodular architecture, and were formed by epithelioid and stellate elements, organized in solid sheets, or embedded in myxoid or chondroid matrix. Areas of osteoid formation were also observed. One tumor had the appearance of classical mixed tumor, showing aspects of duct formation and focal squamous differentiation. Immunohistochemically, all cases were positive for cytokeratins, epithelial membrane antigen, and S100 protein. The expression of other myoepithelial markers, including p63, glial fibrillary acid protein and calponin was more limited. No rearrangement of Ewing sarcoma region 1 (EWSR1) and fused in sarcoma (FUS) genes was observed by fluorescent in situ hybridization. To our knowledge, this is the first report of primary myoepitheliomas of bone arising at juxtacortical sites. These lesions must be distinguished from other benign and malignant bone and cartilage-forming surface tumors, including periosteal chondroma and chondrosarcoma, juxtacortical chondromyxoid fibroma, and periosteal and paraosteal osteosarcoma. The clinicoradiologic presentation and their histological and immunohistochemical features are distinctive enough to allow the separation from these entities.

Prospective study of histomorphometry, biochemical bone markers and bone densitometric response to pamidronate in β‐thalassaemia presenting with osteopenia‐osteoporosis syndrome

This study aimed to evaluate bone remodelling disorders in thalassaemia by using pamidronate (PD) infusion with or without hormone replacement therapy (HRT) as a diagnostic-therapeutic tool. In this prospective study, 24 adult thalassaemia major (TM) and 10 thalassaemia intermedia (TI) patients received either PD and HRT or HRT only (controls) for 3 years. Eugonadal patients with TI had PD only. Bone remodelling was assessed by dual energy X ray absorptiometry (DXA scan), type 1-collagen biochemical bone markers (BBM) and histomorphometry of iliac crest biopsy before and after PD. As a group, thalassaemics had a significant improvement in spinal and femoral bone mineral density Z scores following PD (P < 0·01) compared to the controls. Although BBM were comparable pre-therapy, they were significantly lower in the PD cohort (P < 0·001) compared to the control group. All patients had osteopenia, diminished osteoid formation and bone volume on histomorphometry pre-therapy with high turnover bone disease (HTO) in TM and low-turnover disease (LTO) in TI. In TM, bone volume improved significantly, whereas TI patients showed little or no response to PD. In conclusion, histomorphometry data suggest that TM patients have a distinct pathology of high turnover bone disease compared to TI patients, who have low-turnover disease.

Formononetin reverses established osteopenia in adult ovariectomized rats

Formononetin (Formo) prevents ovariectomy (Ovx)-induced bone loss in rats. However, there are no reports on the curative effects of Formo. The objective of this study was to investigate the ability of Formo in restoring trabecular microarchitecture and promoting new bone formation in osteopenic rats. Adult Sprague-Dawley rats were ovariectomized and left for 90 days for osteopenia to develop. After 90 days, Formo (10.0 mg kg d) was given orally for the next 12 weeks to Ovx rats in a therapeutic protocol. Sham-operated, Ovx + vehicle, and Ovx + parathyroid hormone (PTH) groups served as controls. Trabecular microarchitecture, osteoid formation, bone turnover/resorption markers, and bone osteoprotegerin-to-receptor activator for nuclear κB ligand ratio were studied. One-way analysis of variance was used to test significance of effects. Formo treatment significantly restored the lost trabecular microarchitecture in the femurs and tibia of osteopenic Ovx rats and promoted new bone formation. Formo was devoid of any uterine estrogenicity. Serum levels of type I collagen N-terminal propeptide, which is a reliable marker of bone formation, were increased in Ovx rats treated with Formo compared with Ovx + vehicle group, and the levels were comparable with those in the sham group. Formo prevented the Ovx-induced increase in bone turnover markers, including serum osteocalcin and urinary type I collagen degradation product. Furthermore, Formo-treated Ovx rats had an increased bone osteoprotegerin-to-receptor activator for nuclear κB ligand ratio compared with the Ovx + vehicle group. Daily oral administration of Formo for 12 weeks has a substantial anabolic effect, thus raising the possibility of its use in postmenopausal osteoporosis.

The Effect of Etidronate on the Periodontium of Ovariectomized Rats

Bisphosphonates are indicated for the treatment of osteoporosis. However, they could have an adverse effect on specific sites, such as the bisphosphonate-related osteonecrosis of the jaw. The aim of this study is to investigate the effect of etidronate on the resorption and apposition sides of the periodontium in ovariectomized rats. Twenty-four female Wistar rats were randomly subjected to either ovariectomy or sham operation. After 8 weeks, six animals of each group were sacrificed. The other 12 rats received 5 mg/kg/day etidronate subcutaneously during 4 weeks. Tartrate-resistant acid phosphatase reaction and immunohistochemical staining for receptor activator of nuclear factor-κB (RANK), RANK-ligand (RANKL), osteoprotegerin (OPG), and osteocalcin was performed. Immunoreactivity was evaluated using a semiquantitative analysis. In ovariectomized rats, osteoclasts were noticed in the root socket of molars, including the apposition side of the periodontium, in which RANKL expression was significantly evidenced. In the etidronate-treated group, OPG expression was significantly expressed and osteoclasts that were noticed in the resorption side remained undetected in the apposition side even under ovariectomy. RANK was significantly expressed in ovariectomized rats treated with etidronate. Osteoid formation and osteocalcin expression were described on the alveolar bone surfaces in etidronate-treated rats, with or without ovariectomy. Etidronate has specific site and bone cell actions in the periodontium. It inhibits the osteoclast differentiation induced by ovariectomy in the apposition side of the periodontium but maintains bone formation over all the socket surfaces. Such specificity may be related to the pathogenesis of the bisphosphonate-induced osteonecrosis of the jaw.

Bone Balance within a Cortical BMU: Local Controls of Bone Resorption and Formation

Maintaining bone volume during bone turnover by a BMU is known as bone balance. Balance is required to maintain structural integrity of the bone and is often dysregulated in disease. Consequently, understanding how a BMU controls bone balance is of considerable interest. This paper develops a methodology for identifying potential balance controls within a single cortical BMU. The theoretical framework developed offers the possibility of a directed search for biological processes compatible with the constraints of balance control. We first derive general control constraint equations and then introduce constitutive equations to identify potential control processes that link key variables that describe the state of the BMU. The paper describes specific local bone volume balance controls that may be associated with bone resorption and bone formation. Because bone resorption and formation both involve averaging over time, short-term fluctuations in the environment are removed, leaving the control systems to manage deviations in longer-term trends back towards their desired values. The length of time for averaging is much greater for bone formation than for bone resorption, which enables more filtering of variability in the bone formation environment. Remarkably, the duration for averaging of bone formation may also grow to control deviations in long-term trends of bone formation. Providing there is sufficient bone formation capacity by osteoblasts, this leads to an extraordinarily robust control mechanism that is independent of either osteoblast number or the cellular osteoid formation rate. A complex picture begins to emerge for the control of bone volume. Different control relationships may achieve the same objective, and the ‘integration of information’ occurring within a BMU may be interpreted as different sets of BMU control systems coming to the fore as different information is supplied to the BMU, which in turn leads to different observable BMU behaviors.

Platelet gel: applications in dental regenerative surgery.

Platelet growth factors obtained from platelet-rich plasma (PRP) are used in prosthetic and periodontal regenerative therapy in dentistry. Increased microvascular proliferation in the first 20 days is followed by enhanced osteoblast activity and immature osteoid formation within 3-6 weeks, improving the quality and quantity of newly formed bone tissue. The aim of this study was to evaluate, through three-dimensional X-ray monitoring, the amount of bone obtained after bone regeneration treatment with platelet gel from autologous PRP. Patients eligible for regenerative treatment of atrophic alveolar bone of the maxilla or mandible were studied. The patients' autologous whole blood was collected at the Department of Immunology and Transfusion of San Matteo Hospital for the preparation of platelet gel. The bone at the treated sites was analysed prior to and 4 months after the treatment using the three-dimensional X-ray system Galileos. Over a period of 6 years, 133 patients were treated: 304 implants were inserted and there were five cases of failure. The regenerated bone area consisted of histologically immature osteoid tissue composed of thin trabeculae of vital bone and nuclei of osteocytes, associated with fibro-connective tissue. This co-operative trial between the Transfusion Centre, for standardised production and validation of the platelet gel, and the Dental Surgery room for its application showed that the technique appears effective and safe. Although difficulties were encountered because of the small sample size and the inability to carry out long-term histological controls, the use of small amounts of PRP (5-10%) combined with autologous bone (15-20%) and alloplastic material appears to reduce the need for bone grafting.

Behaviour of ChronOS™ Inject in metaphyseal bone defects of distal radius fractures: Tissue reaction after 6–15 months

Biodegradable calcium phosphate cements are frequently used in human patients but data regarding resorption characteristic of ChronOS™ Inject in metaphyseal bone defects are lacking.Six patients (range 62–81 years) with a dorsally displaced distal radius fracture were treated with volar locking plate systems and ChronOS™ Inject application into the metaphyseal bone defect. During implant removal (time in situ 6–15 months, average 11 months) a 2mm diameter biopsy was obtained from the region of the previous cement injection. In all specimens’ area of bone, osteoid and remaining tissue were histomorphometrically determined and presence of cement particles, bone marrow fibrosis and signs of inflammation were recorded.Vital bone tissue, osteoid formation, mast cell occurrence and marrow fibrosis were detected in most specimens. Varying but small amounts of granular material identified as remainder of the cement were detected in all specimens. Agglomerations of granular material were often surrounded by bone tissue and islets of newly formed osteoid in direct contact with the remaining cement also occurred. Bone density (i.e. area per region of interest) ranged between 6.9% and 36.2% and osteoid density between 0.5% and 7.8%. Bone osteoid ratio was higher in patients who received no osteoporosis medication and lower in patients who received osteoporosis medication (range 6.0–32.1). The present study shows that small amounts of ChronOS™ Inject are still detectable in human patients 15 months after implantation into a distal radius bone defect. During tissue remodelling ChronOS™ Inject is integrated into the newly formed trabecular bone meshwork.

Chondroblastoma-like chondroma of soft tissue: report of the first case in the base of skull

Chondroblastoma-like chondroma (CLC) of soft tissue is a rare benign neoplasm that usually involves the soft tissues of the hand. This report describes the first case of CLC of soft tissue arising in the base of the skull. A 33-year-old man was seen with a slow growing mass in the right parotid region of his face. The noncontrast computed tomographic scans showed an 8.5-cm mass with calcifications involving the right masticator space and extending through the bone into the middle cranial fossa. The radiologic differential diagnosis included osteosarcoma, leiomyosarcoma, chondrosarcoma, and giant cell tumor. During surgery, the large lateral skull base tumor appeared to involve the middle and infratemporal fossae and eroded the surrounding bone. Although the tumor was removed piecemeal, total excision was performed. On microscopic examination, the tumor displayed lobules of mature hyaline cartilage with numerous chondroblasts, coarse calcifications including chicken wire calcifications, and scattered osteoclasts. No atypia, mitoses, necrosis, or osteoid formation was seen. The tumor was diagnosed as chondroma with chondroblastoma features of the soft tissue. His postoperative clinical course was uneventful; however, after 7 months, he had a local recurrence identified on follow-up magnetic resonance imaging. He underwent repeat surgical excision of the tumor, which showed similar histology as the previous excision. This large skull based tumor eroding the bone, which clinically and radiologically mimicked a malignant process, was an unusual presentation of a benign cartilaginous neoplasm. Pathologists should be aware that CLC may occur in the base of the skull and this lesion should be differentiated from the other benign or malignant tumors arising in this area. These lesions have a potential for local recurrence; hence, a close follow-up is recommended.

Stromal-cell-derived factor (SDF) 1-alpha in combination with BMP-2 and TGF-β1 induces site-directed cell homing and osteogenic and chondrogenic differentiation for tissue engineering without the requirement for cell seeding

The clinical translation of tissue engineering approaches is limited by the requirement of a cell source. Cell guidance is a new concept that provides an alternative approach, obviating a requirement for an external cell source. This relies on site-specific homing and differentiation of the patient's own cells to an implanted scaffold through controlled delivery of cytokines. In this study, we used stromal-cell-derived factor 1-alpha (SDF-1α) in combination with bone morphogenic protein (BMP)-2 or transforming growth factor (TGF)-β1 to induce cell migration and osteogenic or chondrogenic differentiation, respectively, in implanted scaffolds in a rat model. A customized cytokine microdelivery apparatus was used to ensure the constant rate and concentration of cytokine delivery around the scaffold. The formation of osteoid or early cartilage was observed after 4weeks in specimens treated with SDF-1α and either BMP-2 or TGF-β1. The density of cellular infiltrate and formation of differentiated tissue were lower in scaffolds treated only with BMP-2 or TGF-β1. Thus, controlled SDF-1α delivery induces cell migration into scaffolds and can result in enhanced osteogenesis and chondrogenesis when used in combination with differentiation cytokines for purposes of tissue engineering.

Effect of bone morphogenetic protein 2 on tendon‐to‐bone healing in a canine flexor tendon model

Tendon-to-bone healing is typically poor, with a high rate of repair-site rupture. Bone loss after tendon-to-bone repair may contribute to poor outcomes. Therefore, we hypothesized that the local application of the osteogenic growth factor bone morphogenetic protein 2 (BMP-2) would promote bone formation, leading to improved repair-site mechanical properties. Intrasynovial canine flexor tendons were injured in Zone 1 and repaired into bone tunnels in the distal phalanx. BMP-2 was delivered to the repair site using either a calcium phosphate matrix (CPM) or a collagen sponge (COL) carrier. Each animal also received carrier alone in an adjacent repair to serve as an internal control. Repairs were evaluated at 21 days using biomechanical, radiographic, and histologic assays. Although an increase in osteoid formation was noted histologically, no significant increases in bone mineral density occurred. When excluding functional failures (i.e., ruptured and gapped repairs), mechanical properties were not different when comparing BMP-2/CPM groups with carrier controls. A significantly higher percentage of BMP-2 treated specimens had a maximum force <20 N compared to carrier controls. While tendon-to-bone healing can be enhanced by addressing the bone loss that typically occurs after surgical repair, the delivery of BMP-2 using the concentrations and methods of the current study did not improve mechanical properties over carrier alone. The anticipated anabolic effect of BMP-2 was insufficient in the short time frame of this study to counter the post-repair loss of bone.

Daily parathyroid hormone 1-34 replacement therapy for hypoparathyroidism induces marked changes in bone turnover and structure.

Parathyroid hormone (PTH) has variable actions on bone. Chronically increased PTH is catabolic and leads to osteoporosis; yet intermittent administration is anabolic and increases bone mass. PTH deficiency is associated with decreased bone remodeling and increased bone mass. However, the effects of PTH replacement therapy on bone in hypoparathyroidism are not well known. We discontinued calcitriol therapy and treated 5 hypoparathyroid subjects (2 adults and 3 adolescents) with synthetic human PTH 1-34 (hPTH 1-34), injected two to three times daily for 18 months, with doses individualized to maintain serum calcium at 1.9 to 2.25 mmol/L. Biochemical markers and bone mineral density (BMD) were assessed every 6 months; iliac-crest biopsies were performed before and after 1 year of treatment. hPTH 1-34 therapy significantly increased bone markers to supranormal levels. Histomorphometry revealed that treatment dramatically increased cancellous bone volume and trabecular number and decreased trabecular separation. Changes in trabecular width were variable, suggesting that the increase in trabecular number was due to the observed intratrabecular tunneling. Cortical width remained unchanged; however, hPTH 1-34 treatment increased cortical porosity. Cancellous bone remodeling was also stimulated, inducing significant changes in osteoid, mineralizing surface, and bone formation rate. Similar changes were seen in endocortical and intracortical remodeling. BMD Z-scores were unchanged at the spine and femoral neck. Total hip Z-scores increased; however, total body BMD Z-scores decreased during the first 6 months of treatment and then stabilized, remaining significantly decreased compared to baseline. Radial Z-scores also decreased with treatment; this was most pronounced in the growing adolescent. Daily hPTH 1-34 therapy for hypoparathyroidism stimulated bone turnover, increased bone volume, and altered bone structure in the iliac crest. These findings suggest that treatment with hPTH 1-34 in hypoparathyroid adults and adolescents has varying effects in the different skeletal compartments, leading to an increase in trabecular bone and an apparent trabecularization of cortical bone.

Gliosarcoma with osseous tissue: an occasional metaplastic component

Glioosarcomas represent a rare entity of intrinsic CNS neoplasms consisting of glial and sarcomatous elements; they account for 2% of glioblastomas. There have been few reports of metaplastic osseous transformation in gliosarcomas. Here we report a rare case of gliosarcoma with metaplastic osteoid in a 57-year-old male patient. Magnetic resonance imaging revealed a large solid cystic heterogeneous mass lesion in the left temporal lobe with peri-tumoral oedema and areas of calcification. Histology revealed a grade IV tumour with neoplastic glial and mesenchymal components with myxoid change and areas of necrosis. The sarcomatous areas contained regions of benign osteoid formation. The histogenesis of the osseous element in gliosarcomas is not well understood, and could be a result of a metaplastic change or divergent differentiation from a common progenitor cell. The osseous tissue may be in the form of newly formed osteoid, benign bone tissue formation with lacunae and osteoblastic rimming, or unequivocally malignant tissue resembling an osteosarcoma.