Aneurysmal bone cyst and osteoblastoma after neoadjuvant denosumab: histologic spectrum and potential diagnostic pitfalls.

The use of denosumab to treat giant cell tumors of bone (GCT) and other giant cell-containing bone tumors has become more common. While the clinicopathologic features of denosumab-treated giant cell tumors of bone have been well-illustrated, descriptions of other denosumab-treated bone tumors are very limited. Surgical pathology files of two institutions and consultation files from two authors were searched for denosumab-treated aneurysmal bone cysts and denosumab-treated osteoblastomas. Clinicopathologic features were reviewed and analyzed. We identified four patients with denosumab-treated bone tumors other than GCT from our surgical pathology and consultation files, including two aneurysmal bone cysts and two osteoblastomas. All were treated with denosumab for 0.5-7.0 (median 4.5) months. Radiologically, denosumab-treated tumors showed decreased size with increased ossification and mineralization on CT and heterogeneous intermediate to hypointense signal on MRI. Histologically, denosumab-treated aneurysmal bone cyst contained thin, elongated, curvilinear, and anastomosing strands of bone with empty lacunae, while denosumab-treated osteoblastoma showed circumscribed nodules of woven bone lined by small osteoblasts. Denosumab-treated aneurysmal bone cyst and osteoblastoma showed treatment-related morphologic changes that can mimic other bone neoplasms. Their recognition requires correlation with the clinical history of denosumab use and radiologic findings.

Ligustilide inhibits the proliferation of human osteoblastoma MG63 cells through the TLR4-ERK pathway.

OBJECTIVE: To study the proapoptotic effect of ligustilide on osteoblastoma (OS) and the relative related molecular mechanism. METHODS AND MATERIALS: An MTT was used to examine the proliferation of OS cells, and Flow cytometry was used to analyze apoptosis and the cell cycle. Western blotting was used to detect the signaling pathway of apoptosis, and immunohistochemical (IH) staining was used to detect the apoptosis status of OS cells. A TLR4 inhibitor was used to study the effect of ligustilide on OS. RESULTS: Ligustilide inhibited OS cell proliferation but had no inhibitory effect on normal bone marrow cells. Flow cytometry results showed that ligustilide induced apoptosis in OS cells, and the cell cycle was arrested at the M/G2 phase. Western blot results showed that ERK, P53, P21, Caspase 9, Caspase 8 and Caspase 3 were all activated; cytochrome C and Bax increased; and Bcl-2 decreased when OS was treated with ligustilide. When an ERK or Caspase inhibitor was added to the culture medium, the apoptosis of OS cells decreased to some degree. When OS cells were pretreated with CLI-095, which is a TLR4 inhibitor, the percentage of apoptotic cells and cell cycle arrest were both reversed. IH results also showed that ligustilide induced apoptosis in OS cells, and the effect was blocked by the TLR4 inhibitor. CONCLUSION: Ligustilide selectively inhibited the proliferation of OS cells by inducing apoptosis, which possibly included endogenous and exogenous apoptosis through TLR4.

Fabrication of Ti + Mg composites by three-dimensional printing of porous Ti and subsequent pressureless infiltration of biodegradable Mg.

A semi-degradable Ti + Mg composite with superior compression and cytotoxicity properties have been successfully fabricated using ink jet 3D printing followed by capillary mediated pressureless infiltration technique targeting orthopaedic implant applications. The composite exhibited low modulus (~5.2 GPa) and high ultimate compressive strength (~418 MPa) properties matching that of the human cortical bone. Ti + Mg composites with stronger 3D interconnected open-porous Ti networks are possible to be fabricated via 3D printing. Corrosion rate of samples measured through immersion testing using 0.9%NaCl solution at 37 °C indicate almost negligible corrosion rate for porous Ti (~1.14 µm/year) and <1 mm/year for Ti + Mg composites for 5 days of immersion, respectively. The composite significantly increased the SAOS-2 osteoblastic bone cell proliferation rate when compared to the 3D printed porous Ti samples and the increase is attributed to the exogenous Mg2+ ions originating from the Ti + Mg samples. The cell viability results indicated absent to mild cytotoxicity. An attempt is made to discuss the key considerations for net-shape fabrication of Ti + Mg implants using ink jet 3D printing followed by infiltration approach.

The Use of Denosumab in Osteoblastoma of the Metacarpal.

Osteoblastoma is a benign aggressive primary bone tumor that occasionally presents in the hand. Because surgical treatment remains the mainstay of treatment, there are no established nonsurgical pharmacological options for patients in whom resection is not feasible. Novel therapies, such as denosumab, are currently being investigated in primary bone tumors. We report a case of osteoblastoma of the first metacarpal that was successfully treated with denosumab. The patient showed a rapid and dramatic response to treatment that led to the transformation of a locally destructive tumor into an ossified painless mass, restoring function while avoiding surgery.

Neoadjuvant denosumab for the treatment of a sacral osteoblastoma.

PURPOSE: To present a case of aggressive sacral osteoblastoma (OB) treated with neoadjuvant denosumab therapy and en bloc resection. METHODS: Case report of a 14-year-old male with an aggressive OB affecting the superior articular process of the left first sacral segment. The lesion was lytic and metabolically active and involved the left-sided posterior elements of S1-S3 with extension into the spinal canal, affecting the left S1, S2, S3, S4 and S5 nerve roots. He was treated for 1 month with neoadjuvant denosumab followed by en bloc resection. RESULTS: Denosumab therapy caused regression of the tumour and converted the diffuse infiltrative mass into a well-defined solid (osteoma-like) structure, aiding surgical resection and preserving the S1, S4 and S5 nerve roots. Histologically, the treated lesion showed abundant sclerotic woven bone and osteoblasts with absence of osteoclasts. CONCLUSIONS: A short course of denosumab caused tumour regression, ossification and conversion of an aggressive OB into a sclerotic, well-defined lesion thus aiding surgical resection and preservation of neural structures. Neoadjuvant therapy reduced osteoclast numbers but PET showed that the lesion remained FDG avid post-therapy.

Bufotalin-induced apoptosis in osteoblastoma cells is associated with endoplasmic reticulum stress activation.

The search for novel and more efficient chemo-agents against malignant osteoblastoma is important. In this study, we examined the potential anti-osteoblastoma function of bufotalin, and studied the underlying mechanisms. Our results showed that bufotalin induced osteoblastoma cell death and apoptosis in dose- and time-dependent manners. Further, bufotalin induced endoplasmic reticulum (ER) stress activation in osteoblastoma cells, the latter was detected by the induction of C/EBP homologous protein (CHOP), phosphorylation of inositol-requiring enzyme 1 (IRE1) and PKR-like endoplasmic reticulum kinase (PERK), as well as caspase-12 activation. Conversely, the ER stress inhibitor salubrinal, the caspase-12 inhibitor z-ATAD-fmk as well as CHOP depletion by shRNA significantly inhibited bufotalin-induced osteoblastoma cell death and apoptosis. Finally, by using a mice xenograft model, we demonstrated that bufotalin inhibited U2OS osteoblastoma cell growth in vivo. In summary, our results suggest that ER stress contributes to bufotalin-induced apoptosis in osteoblastoma cells. Bufotalin might be investigated as a novel anti-osteoblastoma agent.

Osteoblastoma response to radiotherapy and chemotherapy.

Osteoblastoma is a rare primary bone tumor that is curable by complete excision. There are few data about the effectiveness of chemotherapy or radiotherapy in the treatment of recurrent osteoblastoma. We report a 13-year-old girl wit recurrent osteoblastoma who, after in complete surgical excision, responded to treatment with radiotherapy and later with chemotherapy. Surgery remains the treatment of choice for osteoblastoma. Radiotherapy and chemotherapy either alone or together may be useful in selected patients with recurrent, aggressive tumor or in patients with surgically unresectable disease.

Tumores agresivos de la rodilla. Tratamiento con cirugía amplia y clavo centromedular / Agressive bone tumors around the knee. treatment by wide resection and intramedullary loking nailing

Se presentan retrospectivamente los resultados de 31 pacientes con tumores óseos, con lesiones que variaron de benignas agresivas a malignas de bajo y alto grado, tratadas con cirugía amplia, artrodesis con clavo centromedular macizo femorotibial de tamaño especial fijo al hueso por pernos, e injerto autónomo hemicilíndrico. El diagnóstico histopatológico fue de tumor de células gigantes en 22 casos (70.96 por ciento), de los cuales 16 correspondieron a lesiones benignas agresivas y 6 a malignas de bajo grado, 2 histiocitomas fibrosos malignos (6.45 por ciento), 2 sarcomas radioinducidos (6.45 por ciento), 1 osteosarcoma (3.22 por ciento), 1 osteoblastoma (3.22 por ciento), 1 condrosarcoma (3.22 por ciento), 1 fibrosarcoma (3.22 por ciento) y un fibroma desmoplástico (3.22 por ciento). Los casos de histiocitoma fibroso maligno se manejaron con el esquema de quimioterapia con vincristina 0.5 mg, epirrubicina 75 mg, y ciclofosfamida 600 mg todo por metro cuadrado de superficie corporal. En el sarcoma osteogénico se usaron dosis altas de metotrexato a 5 g/m² de superficie corporal. El periodo de seguimiento fue de 6 a 96 meses (x=52.6 meses), obteniéndose buenos resultados al conseguirse, el control satisfactorio del tumor, buena rehabilitación dentro de las limitaciones de la artrodesis de la rodilla, la marcha a los 5 días del postoperatorio, la ausencia de recidivas y adecuada aceptación psicológica por la conservación de la extremidad