Osteolytic Metastases Research Articles

Pharmacological Inhibition of Signaling through the Activin Receptor Type IIa Prevents Primary Tumor Growth and Skeletal Metastases in Mouse Models of Breast Cancer.

Abstract Breast cancer cells have a strong propensity to metastasize to bone, resulting in debilitating complications such as intractable bone pain, spinal compression, pathological fractures, or loss of mobility and function. Anti-resorptive agents, such as bisphosphonates, are commonly used to halt the loss of bone, but do not stimulate the formation of new bone. Previous data demonstrated that treatment with an activin antagonist, a soluble form of the extracellular domain of the activin receptor type IIA (ActRIIA) fused to a murine IgG-Fc fragment (RAP-011), can restore bone mass in ovariectomized mice with established bone loss and prevent bone loss in a murine model of multiple myeloma.The goal of the current studies was to establish the ability of RAP-011 to directly inhibit breast cancer cell proliferation, delay primary tumor growth and prevent skeletal metastases. Bioluminescent breast cancer cells (MCF-7-luc and MDA-MB-231-luc-D3H2LN) were administered orthotopically to establish a primary tumor model or by intracardiac injection to establish a metastatic breast cancer model. Both studies were performed using athymic nude mice that had been pretreated for 2 weeks with RAP-011 (10 mg/kg S.C. twice weekly) or vehicle (VEH).In vitro studies demonstrated that activin A stimulated proliferation of some tumor cell lines, while the addition of soluble ActRIIa blocked the stimulation. In the orthotopic models of breast cancer RAP-011 treated mice had significantly smaller primary tumors as early as 3 weeks post-inoculation. RAP-011 treated mice had tumors that remained significantly smaller for the duration of the 10 week study (-60%, p<0.02).In the model of metastatic breast cancer, RAP-011 treated mice displayed lower levels of hind limb, mandible and lung metastases compared to VEH-treated mice. RAP-011 treated mice had reduced tumor burden (-70%, p<0.001), fewer osteolytic lesions (-45%, p<0.05) and increased overall survival by 11 days compared to VEH-treated mice. DXA scanning of the mice revealed RAP-011 treated mice had a significant increase in bone mineral density compared to the VEH treated mice (+10%, p<0.05), reflecting the decreased levels of osteolytic metastases. Histological analysis of the femur and tibia confirmed increased levels of tumor growth and osteolytic lesions, as well as decreased levels of trabecular bone volume in VEH treated mice.These data support the role of Activin in the establishment and growth of tumors and that the use of a soluble ActRIIA receptor can prevent primary tumor growth and inhibit metastases in patients with breast cancer. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 5058.

Abstract B108: Inhibition of osteoblastic tumorigenesis of a novel human prostate cancer cell line by the blockade of TGF-β signaling

Abstract The skeleton is the most common site of prostate cancer metastasis, which often results in osteoblastic lesions. The associated fractures and pain are major causes of morbidity and mortality in prostate cancer patients. Transforming growth factor-beta (TGFβ) signaling has been shown to developmentally regulate bone mass and bone matrix properties. It has also been shown to promote osteolytic metastasis induced by breast cancer through its regulation of some secreted proteins that are involved in bone resorption. However, its role in prostate cancer-induced osteoblastic metastasis is much less clear. This is in part due to a lack of prostate cancer cell lines that can efficiently induce bone metastasis and osteoblastic lesions in animal models. We found that a newly established human prostate cancer PacMetUT1 cell line produces copious amounts of active TGFβ1 and induces extensive bone metastases in calvaria, rib, femur, and tibia when inoculated in the left cardiac ventricle of male nude mice. Histology revealed extensive bone formation in the metastatic lesions of the calvaria and femur with some areas showing bone resorption. Stable knockdown of TGFβ1 with a shRNA in the PacMetUT1 cells resulted in significantly reduced TGFβ1 secretion and decreased tumor incidence when the cells were directly injected into the tibiae of male nude mice. Systemic administration of either a small inhibitor of TGFβ type I receptor kinase or a pan TGFβ binding protein also decreased osteoblastic intratibial tumor incidence and growth. PacMetUT1 is a novel prostate cancer cell line for the investigation of mechanisms that regulate formation of metastatic osteoblastic bone lesions. Future studies will reveal whether targeting the TGFβ signaling pathway is feasible for the prevention and treatment of prostate cancer-induced bone metastasis. Citation Information: Mol Cancer Ther 2009;8(12 Suppl):B108.

Osteoplastie in Kombination mit der Radiofrequenzablation zur palliativen Therapie schmerzhafter osteolytischer Knochenmetastasen

Osteolytic metastases are a challenging problem in cancer patients. Moreover, these patients are increasing because primary tumours are well controlled by recent advances in primary cancer treatments. Nevertheless, pain relief and bone stabilization are the priorities for most cancer patients with painful bone metastases and pathological vertebral fractures. Until now, treatments for bone metastases have been mainly conservative, such as radiation therapy, chemotherapy, or analgetics. Additionally vertebroplasty and osteoplasty has been widely used in these patients. Recently, a new technique that combines RF ablation therapy followed by percutaneous cement injection has shown to be effective when bone metastases become bulky, extend outside bones or in metastastic lesions with epidural extension and cortical disruption.

A Bone Metastasis Model With Osteolytic and Osteoblastic Properties of Human Lung Cancer ACC-LC-319/bone2 in Natural Killer Cell-Depleted Severe Combined Immunodeficient Mice

Lung cancer is commonly associated with multiple-organ metastasis, and bone is a frequent metastatic site for lung cancer. Lung cancer frequently develops osteolytic, and less frequently osteoblastic, metastasis to bone. Osteolytic metastasis models of lung cancer have been reported, but no osteoblastic metastasis model is available for lung cancer. In the present study, we established a reproducible model of human lung cancer with both osteolytic and osteoblastic changes in natural killer cell-depleted severe combined immunodeficient mice. Intravenous inoculation of ACC-LC-319/bone2 cells resulted in the development of metastatic colonies in the lung, liver, and bone of the mice. As assessed sequentially by X-ray photographs, osteolytic bone lesions were observed by day 28, and then osteoblastic lesions were detected by day 35. Histological examination revealed the presence of bony spurs, a hallmark of osteoblastic bone metastasis, where osteoclasts were hardly observed. Treatment with an anti-human vascular endothelial growth factor antibody, bevacizumab, as well as zoledronate, inhibited the number of experimental bone metastases, including osteoblastic changes produced by ACC-LC-319/bone2 cells. These results indicate that our bone metastasis model by ACC-LC319/bone2 might be useful to understand the molecular pathogenesis of osteolytic and osteoblastic metastasis, and to identify molecular targets to control bone metastasis of lung cancer.

Relaxin stimulates osteoclast differentiation and activation

Relaxin is a pleiotropic hormone with actions in reproductive and non-reproductive tissues, and has a role in tumor biology. It can promote growth, differentiation and invasiveness of different tumors, especially those that give bone metastases, and relaxin serum concentrations are increased in patients with bone metastasis. In osteolytic metastasis the destruction of bone is mediated by osteoclasts that are multinucleated cells derived from hematopoietic progenitors. We found that human hematopoietic precursors and mature osteoclasts express the relaxin receptor RXFP1. Then, we investigated the effects of relaxin on the differentiation, activation and gene expression of osteoclasts during in vitro osteoclastogenesis from human hematopoietic progenitor cells. Relaxin alone was able to induce the multistep differentiation process of human osteoclastogenesis with timing similar to that obtained with the classical stimulators of osteoclastogenesis RANKL, M-CSF and PTH. The expression profile of several osteoclast genes was studied with quantitative RT-PCR during the entire process of osteoclastogenesis. This analysis showed that relaxin induced genes that are implicated in the differentiation, survival and activation of osteoclasts. Relaxin-induced osteoclasts were fully differentiated, positive for tartrate resistant acid phosphatase and vitronectin receptor, expressing a typical F-actin ring and able to resorb the bone. Furthermore, relaxin induced the expression of its specific receptor RXFP1 in osteoclasts. This study demonstrates for the first time that relaxin is a potent stimulator of osteoclastogenesis from hematopoietic precursors and regulates the activity of mature osteoclasts, opening new perspectives on the role of this hormone in bone physiology, diseases and metastasis.

Humeral Metastasis in Patients with Stage IV Non-Small–Cell Lung Cancer Portends a Short Life Expectancy

Journal of Palliative MedicineVol. 12, No. 10 Letters to the EditorHumeral Metastasis in Patients with Stage IV Non-Small–Cell Lung Cancer Portends a Short Life ExpectancyFederico Ampil and Roxana BalunaFederico AmpilSearch for more papers by this author and Roxana BalunaSearch for more papers by this authorPublished Online:6 Oct 2009https://doi.org/10.1089/jpm.2009.0155AboutSectionsPDF/EPUB Permissions & CitationsPermissionsDownload CitationsTrack CitationsAdd to favorites Back To Publication ShareShare onFacebookTwitterLinked InRedditEmail "Humeral Metastasis in Patients with Stage IV Non-Small–Cell Lung Cancer Portends a Short Life Expectancy." , 12(10), pp. 869–870FiguresReferencesRelatedDetailsCited byAn Osteolytic Metastasis of Humerus from an Asymptomatic Squamous Cell Carcinoma of Lung: A Rare Clinical EntityCase Reports in Pulmonology, Vol. 2014 Volume 12Issue 10Oct 2009 InformationCopyright 2009, Mary Ann Liebert, Inc.To cite this article:Federico Ampil and Roxana Baluna.Humeral Metastasis in Patients with Stage IV Non-Small–Cell Lung Cancer Portends a Short Life Expectancy.Journal of Palliative Medicine.Oct 2009.869-870.http://doi.org/10.1089/jpm.2009.0155Published in Volume: 12 Issue 10: October 6, 2009PDF download

Osteolytic prostate cancer cells induce the expression of specific cytokines in bone-forming osteoblasts through a Stat3/5-dependent mechanism

Prostate cancer primarily metastasizes to bone, and the interaction of cancer cells with bone cells results in a local activation of bone formation and/or bone resorption. Since the cellular and molecular mechanisms underlying the development of these tumor-induced osteoblastic or osteolytic lesions are still poorly understood, we have compared the effects of two prostate cancer cell lines, osteoblastic MDA-PCa-2b cells and osteolytic PC-3 cells, on bone-forming osteoblasts. Using Affymetrix Gene Chip hybridization followed by qRT-PCR confirmation we were able to identify specific genes, including Smpd3 and Dmp1, whose expression is significantly reduced upon treatment with PC-3-conditioned medium. Moreover, we observed that PC-3-conditioned medium led to a marked induction of several cytokine genes, including Cxcl5, Cxcl12 and Tnfsf11, the latter one encoding for the osteoclast differentiation factor Rankl. Likewise, when we analyzed the effects of MDA-PCa-2b- and PC-3-conditioned medium on signal transduction in osteoblasts we did not only observe opposite effects on the canonical Wnt signalling pathway, but also a specific induction of Erk and Stat phosphorylation by PC-3-conditioned medium. Most importantly, the induction of Cxcl5, Cxcl12 and Tnfsf11 in osteoblasts by PC-3-conditioned medium was abrogated by the Stat3/5 inhibitor piceatannol, whereas the selective blockade of Stat1 and Erk activation had no effect. Together with the finding, that activated Stat3 in osteoblasts was detectable in bone biopsies from patients with osteolytic metastases, our data suggest that the Stat3/5-dependent activation of cytokine expression in osteoblasts may have a significant impact on cancer cell migration and proliferation, but also on osteoclast activation.

Balloon kyphoplasty in malignant spinal fractures: a systematic review and meta-analysis.

BackgroundSpinal fractures are a common source of morbidity in cancer patients. Balloon Kyphoplasty (BKP) is a minimally invasive procedure designed to stabilize fractures and correct vertebral deformities. We performed a meta-analysis to determine the efficacy and safety of BKP for spinal fractures in cancer patients.MethodsWe searched several electronic databases up to September 2008 and the reference lists of relevant publications for studies reporting on BKP in patients with spinal fractures secondary to osteolytic metastasis and multiple myeloma. Outcomes sought included pain relief, functional capacity, quality of life, vertebral height, kyphotic angle and adverse events. Studies were assessed for methodological bias, and estimates of effect were calculated using a random-effects model. Potential reasons for heterogeneity were explored.ResultsThe literature search revealed seven relevant studies published from 2003 to 2008, none of which were randomized trials. Analysis of those studies indicated that BKP resulted in less pain and better functional outcomes, and that these effects were maintained up to 2 years post-procedure. While BKP also improved early vertebral height loss and spinal deformity, these effects were not long-term. No serious procedure-related complications were described. Clinically asymptomatic cement leakage occurred in 6% of all treated levels, and new vertebral fractures in 10% of patients. While there is a lack of studies comparing BKP to other interventions, some data suggested that BKP provided similar pain relief as vertebroplasty and a lower cement leakage rate.ConclusionIt appears that there is level III evidence showing BKP is a well-tolerated, relatively safe and effective technique that provides early pain relief and improved functional outcomes in patients with painful neoplastic spinal fractures. BKP also provided long-term benefits in terms of pain and disability. However, the methodological quality of the original studies prevents definitive conclusions being drawn. Further investigation into the use of BKP for spinal fractures in cancer patients is warranted.

Pancreatic cancer's initial presentation: back pain due to osteoblastic bone metastasis

Pancreatic cancer may cause osteolytic metastases, but the osteoblastic ones are extremely rare. In addition, it almost always presents with symptoms related to the invasion of the structures in the abdomen. Symptoms from bone metastases are rare and, if seen, are in the late phase of the course. We present a case of cancer of the body of the pancreas, which presented with severe back pain due to an osteoblastic lesion to L3 vertebra. Biopsy of the vertebra led to the diagnosis. Radiographs, computed tomography, magnetic resonance and scintigraphic images as well as pathology slices are shown. The present case raises the issue that pancreatic cancer, as a cause of an osteolytic bone lesion, should not be overlooked in an unknown primary investigation.

The treatment of metastasis to the femoral neck using percutaneous hollow perforated screws with cement augmentation

We have developed a hollow perforated cannulated screw. One or more of these was implanted percutaneously in 11 patients with an osteolytic metastasis in the femoral neck and multiple metastases elsewhere. They were supplemented by one or two additional standard 6.5 mm cannulated screws in nine patients. Polymethylmethacrylate bone cement was injected through the screw into the neck of the femur using small syringes, as in vertebroplasty. The mean amount of cement injected was 23.2 ml (17 to 30). Radiotherapy was started on the fourth post-operative day and chemotherapy, on average, was resumed a day later. Good structural stability and satisfactory relief from pain were achieved in all the patients. This technique may be useful in the palliation of metastases in the femoral neck.

Enhanced expression and shedding of receptor activator of NF-κB ligand during tumor–bone interaction potentiates mammary tumor-induced osteolysis

The bone microenvironment plays a critical role in tumor-induced osteolysis and osteolytic metastasis through tumor-bone (TB)-interaction. Receptor activator of nuclear factor-kappaB (RANK) ligand (RANKL) is one of the critical signaling molecules involved in osteolysis and bone metastasis. However, the regulation and functional significance of RANKL at the TB-interface in tumor-induced osteolysis remains unclear. In this report, we examined the role of tumor-stromal interaction in the regulation of RANKL expression and its functional significance in tumor-induced osteolysis. Using a novel mammary tumor model, we identified that RANKL expression was upregulated at the TB-interface as compared to the tumor alone area. We demonstrate increased generation of sRANKL at the TB-interface, which is associated with tumor-induced osteolysis. The ratio of RANKL to osteoprotegrin (OPG), a decoy receptor for RANKL, at the TB-interface was also increased. Targeting RANKL expression with antisense oligonucleotides (RANKL-ASO), significantly abrogated tumor-induced osteolysis, decreased RANKL expression and the RANKL:OPG ratio at the TB-interface. Together, these results demonstrate that upregulation of RANKL expression and sRANKL generation at the TB-interface potentiates tumor-induced osteolysis.

Pathological Vertebral Compression Fracture of C3 Due to a Breast Cancer Metastasis in a Male Patient

A case of vertebral body fracture due to metastatic breast cancer in a male patient and a review of the literature are presented. To draw attention to the possible adverse skeletal events in breast cancer patients, and the need of a watchful staff within the multidisciplinary team in charge. Breast cancer is a rare condition in men, the male/female ratio is 1 of 100 approximately; in both sexes bone metastases are the most common. The pathologic fracture by spinal metastases can cause intense pain with difficult management. Vertebroplasty has been used successfully to treat pain and improve functional status in patients with vertebral compression fractures due to metastases. A 43-year-old male patient was diagnosed of having breast epithelial carcinoma after histologic analysis of a femur fracture. Following reconstruction, the patient started rehabilitative treatment. In a control visit, he referred sudden cervical pain which was initially treated with nonsteroidal anti-inflammatory drugs and rest. The patient was seen in a later visit and complained about poor response to analgesia. For this reason, a radiologic study was carried out, showing signs of fracture of the third cervical vertebral body (C3), and was completed with magnetic resonance imaging where the diagnosis of osteolytic metastasis was confirmed. After consulting the interventionist radiology team, vertebroplasty was carried out aiming to diminishing the pain. There were no postoperative complications and the patient's recovery from cervicalgia permitted the nonsteroidal anti-inflammatory drugs suspension. Two weeks after the vertebroplasty, the patient resumed his rehabilitative treatment without presenting cervical pain or mobility limitation. Spinal metastases treatment may include combinations of radiotherapy, vertebroplasty, and bisphosphonates, which have proved analgesic effect and a decrease of bone complications; however, out of these options, only vertebroplasty allows rapid stabilization and analgesia.

Long-term efficacy and safety of pamidronate disodium in treatment of bone metastases in breast cancer

ObjectiveTo evaluate the long-term efficacy and safety of pamidronate disodium in patients with bone lesions secondary to advanced breast carcinoma.MethodsA retrospective chart review was conducted of 62 patients receiving intravenous pamidronate disodium for metastatic breast cancer. The proportion of patients experiencing at least one skeletal related event (SRE) after 12 months of therapy was determined.ResultsThe proportion of patients who had an SRE was 29.00% (18 individuals) and the median time to first event was greater than 350 days. Radiotherapy(11 individuals)and pathologic fracture(6 individuals)were the most frequent type of SRE, while cord compression(1 individuals) and hypercalcaemia(0 individuals) were rare. A total of 37 individuals had transient hypocalcaemia without any clinical symptom. No significant creatinine abnormalities were encountered. There were no clinically relevant changes of calcium, phosphate and creatinine before and after therapy.ConclusionLong-term treatment with pamidronate disodium significantly reduces and delays skeletal morbidity from osteolytic metastases. Prolonged therapy was well tolerated. This study suggests that the rate of clinically relevant SREs is substantially lower than the event rate observed in phase III clinical trials.

Do not use bisphosphonates without scientific evidence, neither in treatment nor prophylactic, in the treatment of stress fractures

Stress fractures are common in athletes and can end the career because of its long time for healing [1, 2, 4, 5, 14]. In military recruits, especially in basic training, it has led to modification of the type of training, the time for the repetitions and the load [9, 10]. The researchers are trying hard to get a solution to the problem, not only with different types of surgery but also by medical treatment [4, 11]. Bisphosphonates have been used for several years to treat osteoporosis by its function to increase bone mass and decrease fracture risk as the osteoclast activity depresses [8]. It is a potent drug, used in the treatment of severe diseases like Paget’s disease, bone tumors and metastases. A stress fracture is an overuse injury and the mechanism depends on the load of the bone and if the load gives more strain and strain rate than the bone can stand, then a stress fracture occur [10]. Animal model experiments have suggested that suppression of bone remodeling can prevent stress fractures [2, 3, 8]. There are contradictive signals whether it is possible or not to detect any biochemical markers in the blood of recruits or athletes with increased bone remodeling as a sign for stress fracture [1]. The effect of bisphosphonates on fracture healing has also been discussed, though they suppress bone remodeling—some researchers have reported larger callus and delayed maturation of the fracture in animal models and some other report no problem with fracture callus remodeling unless very high doses of bisphosphonates are used [7, 8]. On the contrary, other reports propose that bisphosphonates may enhance fracture repair, probably by stabilizing the fracture callus. Others include the improved osseointegration of metal implants in treated ovariectomized rats, or improved distraction osteogenesis, conserving bone architecture after osteonecrosis [6]. Bisphosphonates are known to reduce pain in different bone conditions as osteolytic metastasis, multiple myeloma, and localized transient osteoporosis [15]. A report of one female runner with LTO of the navicular bone, treated with bisphosphonates—were pain—free after few days and then she had a complete resolution of the oedema in the tarsal navicular. This is though only one case [12]. In fatigue loading, no studies using bisphosphonates have proven any effect, but conclusions are that longer treatment than 2 weeks are needed to get effect on fatigue, and a combination of glucocorticoid and alendronate in mice, lowered the apoptotic effect of bisphosphonates on osteoclasts. The half-life of bisphosphonates in bone is very long—1 to 10 years, and depends on the rate of bone remodeling, it is also suggested that bisphosphonates buried in the bone, is inactive, at least as long as it is sequestered there. Alendronate has been shown to inhibit normal microdamage repair that arises from a marked suppression of bone remodeling, which in turn results in accumulation of microdamage. The doses were much higher than those to treat human osteoporosis [13]. Some studies shows that long-term use of bisphosphonates for osteoporosis therapy appears to be safe, however, there are studies that reveal deficiencies in bone formation, and some studies suggest that bisphosphonates treatment I. Ekenman (&) Kungstensg 59, 113 29 Stockholm, Sweden e-mail: Ingrid.ekenman@telia.com

Solitary Tibial Osteolytic Lesion

We report an unusual case of solitary osteolytic tibial metastasis from a primary endometrial cancer in a 62-year-old woman. The primary cancer was treated with total abdominal hysterectomy and bilateral salpingo-oophorectomy combined with postoperative external beam radiotherapy, while the tibial metastasis was treated with an above knee amputation. The rarity of the case lies on the fact that metastases distally to the elbow and knee are uncommon and endometrial cancer rarely gives distal bone metastases and particularly solitary to the extremities.

Plasma-mediated radiofrequency ablation followed by percutaneous cementoplasty under fluoro-CT guidance: a case report

We report a case of a 81-year-old Caucasian man with colorectal carcinoma, treated by surgery in 1998, referred for palliative treatment of a refractory painful caused by osteolytic metastases of 2.5 cm in back-upper ilium spine. Plasma-mediated radiofrequency ablation was performed under conscious sedation, using Fluoroscopic Computer Tomography guidance. After completing the ablation phase of the procedure, a mixture of bone cement and Biotrace sterile barium sulfate was injected into the ablated cavity.Patient was evaluated by using the Brief Pain Inventory and considering pain interference with daily living at day 1 and 3 and week 1, 2, 3, 4 by means of a telephone interview. A post-procedure Computer Tomography scan was performed to examine the distribution of cement deposition few minutes after the procedure. The plasma mediated RFA and cementoplasty were well tolerated by the patient who did not develop any complication.

Percutaneous polymethylmethacrylate vertebroplasty in the treatment of pain induced by metastatic spine tumor

Background Metastases to the spine are a common problem in the large oncology center and represent a challenging problem in oncology practice. Patients with osteolytic metastases often experience intractable local and/or radicular pain. Therapeutic intervention can alleviate pain, preserve or improve neurologic function, achieve mechanical stability, and improve quality of life. Percutaneous polymethylmethacrylate vertebroplasty is an effective and relatively easy method of relieving patients' pain. Method Between January 2002 and December 2006, 57 patients (78 vertebrae) with spinal metastatic tumor treated with PMMA vertebroplasty were enrolled in this study. The main indication for treatment was pain. Result The mean value of VAS was 8.1 ± 0.67 preoperatively, and it significantly decreased to 3.8 ± 1.9 (1-8, P < .015) 1 day after vertebroplasty. The mean VAS value 6 months after vertebroplasty was 2.8 ± 2.0 ( P < .001). The mean amounts of preoperative nonnarcotic analgesic and narcotic analgesic were 1.98 ± 1.4 and 1.19 ± 0.73, respectively. Postoperatively, the mean amounts of nonnarcotic and narcotic analgesic decreased to 1.35 ± 0.70 ( P < .05) and 0.65 ± 0.53 ( P < .05). A statistically significant reduction of nonnarcotic analgesic use was noticed in our study. Conclusions Percutaneous vertebroplasty is a minimally invasive procedure that offers a remarkable advantage of effective and immediate pain relief with few complications.

Minimally Invasive Vertebroplasty in the Treatment of Pain Induced by Spinal Metastatic Tumor

Spinal metastatic tumor is a common problem and represents a challenging problem in oncology practice. Patients with osteolytic metastases often suffer from intractable local and/or radicular pain. Percutaneous vertebroplasty is a minimally invasive, radiologically guided procedure whereby bone cement is injected into structurally weakened vertebrae to provide immediate biomechanical stability. Vertebroplasty is also used to relieve pain by stabilizing metastatically compromised vertebrae that are at risk of pathological burst fracture. In this retrospective study, a total of 57 patients (78 vertebrae) with spinal metastatic tumor were treated with PMMA vertebroplasty. The mean value of the visual analogue scale (VAS) was 8.1 +/- 0.67 preoperatively, and significantly decreased to 3.8 +/- 1.9 (1-8, p < 0.015) one day after vertebroplasty. The mean VAS value 6 months after vertebroplsty was 2.8 +/- 2.0 (p < 0.001). Mean injected bone cement amount in our study is 5.16 +/- 1.6 mL. The complication rate is about 21.8%, bone cement extravasation without neurological deficit is the most common complication. No new or adjacent vertebral fracture has occurred in more than 2 years follow-up. Percutaneous vertebroplasty is a minimally invasive procedure that offers a remarkable advantage of effective and immediate pain relief with few complications.

Targeted overexpression of BSP in osteoclasts promotes bone metastasis of breast cancer cells

Bone is one of the most common sites of breast cancer metastasis while bone sialoprotein (BSP) is thought to play an important role in bone metastasis of malignant tumors. The objective of this study is to determine the role of BSP overexpression in osteolytic metastasis using two homozygous transgenic mouse lines in which BSP expression is elevated either in all the tissues (CMV-BSP mice) or only in the osteoclasts (CtpsK-BSP mice). The results showed that skeletal as well as systemic metastases of 4T1 murine breast cancer cells were dramatically increased in CMV-BSP mice. In CtpsK-BSP mice, it was found that targeted BSP overexpression in osteoclasts promoted in vitro osteoclastogenesis and activated osteoclastic differentiation markers such as Cathepsin K, TRAP and NFAT2. MicroCT scan demonstrated that CtpsK/BSP mice had reduced trabecular bone volume and bone mineral density (BMD). The real-time IVIS Imaging System showed that targeted BSP overexpression in osteoclasts promoted bone metastasis of breast cancer cells. The osteolytic lesion area was significantly larger in CtpsK/BSP mice than in the controls as demonstrated by both radiographic and histomorphometric analyses. TRAP staining demonstrated a twofold increase in the number of osteoclasts in the bone lesion area from CtpsK/BSP mice compared with that from wild type mice. We conclude that host tissue-derived BSP also plays important roles in breast cancer metastasis through inducing tumor cell seeding into the remote host tissues. Furthermore, osteoclast-derived BSP promotes osteoclast differentiation in an autocrine manner and consequently promotes osteolytic bone metastasis of breast cancer.

Aggressive Adenoid Cystic Carcinoma With Asymptomatic Spinal Cord Compression Revealed By A “Curtain Sign”

The authors present a case of unusually aggressive adenoid cystic carcinoma of the head and neck. The patient presented with sciatica one year after initial diagnosis. She was otherwise asymptomatic. Complete work-up for bone involvement, included bone scan and MRI. The patient had painful osteolytic sacral metastasis and asymptomatic thoracic (T5) vertebral metastasis revealed by a typical curtain sign on MRI. The curtain sign, originally described by Trolard, is due to the displacement of the Trolard's membrane with the median ligament attaching the dura to the bone while there is a dorsal displacement and loosening of the posterior longitudinal ligament. The patient benefited from radiotherapy and did not develop respiratory distress, paraplegia or pain but died of liver metastases.