Assessment of Bone Health Awareness and Education in Breast Cancer Patients with Bone Metastasis in the USA.

Bone metastases are common in advanced breast cancer (BC) patients and increase the risk for skeletal-related events (SREs), which present a significant health and economic burden. Bone targeting agents (BTAs) can improve health-related quality of life by delaying or preventing SREs; nevertheless, a significant portion of eligible BC patients are not receiving this therapy. A bone health education needs assessment survey was conducted to examine cancer-related bone health awareness and to identify opportunities to improve bone health education. Direct-to-patient outreach was used to recruit adult BC patients in the USA self-reporting a diagnosis of bone metastasis within the past 3 years. Of the 200 patients, 59% experienced at least one SRE prior to survey participation (44% radiation to bone, 29% bone fracture, 17% spinal cord compression, 15% surgery to bone), and 83% were currently receiving a BTA. Awareness of general cancer bone health, protection strategies against SREs, and screening tests were low to moderate. Patients currently not receiving a BTA were least knowledgeable about cancer bone health, with only 40% aware of BTAs as a protective strategy, and only 26% were very or extremely satisfied with the information received from healthcare providers. Sixty-two percent of patients wanted to receive information by more than one mode of communication. Notable gaps in bone health education were observed in bone metastatic BC patients at risk for SREs, suggesting the need for earlier and more effective communication and education strategies to promote appropriate BTA use and better health outcomes.

Real-world incidence of symptomatic skeletal events and bone-modifying agent use in castration-resistant prostate cancer - an Australian multi-centre observational study.

INTRODUCTION: Bone metastases occur frequently in castration-resistant prostate cancer (CRPC) and may lead to skeletal-related events (SREs), including symptomatic skeletal events (SSEs). Bone-modifying agents (BMAs) delay SREs and SSEs. However, the real-world use of BMAs is debated given the absence of demonstrated survival advantage and potential adverse events (AEs). Our retrospective study examined BMA use and SSE rates in Australian patients with CRPC. METHODS: Patients with CRPC and bone metastases were identified from the electronic CRPC Australian Database. Patient characteristics, treatment patterns and AEs were analysed. Descriptive statistics reported baseline characteristics, SSE rates and BMA use. Comparisons between groups used t-tests and Chi-square analyses. Overall survival was calculated by the Kaplan-Meier method. RESULTS: A total of 532 eligible patients were identified with a median age of 73 years (range: 44-97 years). BMAs were prescribed in 232 men (46%), 183 of whom received denosumab. Patients receiving first-line docetaxel for CRPC were more likely to commence BMAs than those receiving abiraterone or enzalutamide (51% vs 31% vs 38%; p = 0.004). SSEs occurred in 148 men (28%), most commonly symptomatic lesions requiring intervention (75%). At the time of initial SSEs, only 28% were receiving BMAs. Patients treated at sites with lower BMA use (

[Bone metastasis: Efficacy and technical modalities of classical radiotherapy]. / Métastases osseuses : efficacité et modalités de prescription de la radiothérapie classique.

Conventional radiotherapy is a pivotal treatment in the management of bone metastasis. It is indicated primarily for palliative, analgesic, or decompressive purposes and in the prevention of severe bone events such as fractures and spinal cord compressions. It should be performed as early as possible from the onset of symptoms or within 14days following a surgical procedure of decompression or bone stabilization. Except in some cases, a pattern of 8Gy single dose is currently recommended, possibly renewable, by being vigilant on associated treatments which some, like antiangiogenics, must be imperatively suspended.

Radiation Disrupts the Protective Function of the Spinal Meninges in a Mouse Model of Tumor-induced Spinal Cord Compression.

BACKGROUND: Recent advances in multidisciplinary treatments for various cancers have extended the survival period of patients with spinal metastases. Radiotherapy has been widely used to treat spinal metastases; nevertheless, long-term survivors sometimes undergo more surgical intervention after radiotherapy because of local tumor relapse. Generally, intradural invasion of a spinal tumor seldom occurs because the dura mater serves as a tissue barrier against tumor infiltration. However, after radiation exposure, some spinal tumors invade the dura mater, resulting in leptomeningeal dissemination, intraoperative dural injury, or postoperative local recurrence. The mechanisms of how radiation might affect the dura have not been well-studied. QUESTIONS/PURPOSES: To investigate how radiation affects the spinal meninges, we asked: (1) What is the effect of irradiation on the meningeal barrier's ability to protect against carcinoma infiltration? (2) What is the effect of irradiation on the meningeal barrier's ability to protect against sarcoma infiltration? (3) What is the effect of irradiation on dural microstructure observed by scanning electron microscopy (SEM)? (4) What is the effect of irradiation on dural microstructure observed by transmission electron microscopy (TEM)? METHODS: Eighty-four 10-week-old female ddY mice were randomly divided into eight groups: mouse mammary tumor (MMT) implantation 6 weeks after 0-Gy irradiation (nonirradiation) (n = 11), MMT implantation 6 weeks after 20-Gy irradiation (n = 10), MMT implantation 12 weeks after nonirradiation (n = 10), MMT implantation 12 weeks after 20-Gy irradiation (n = 11), mouse osteosarcoma (LM8) implantation 6 weeks after nonirradiation (n = 11), LM8 implantation 6 weeks after 20-Gy irradiation (n = 11), LM8 implantation 12 weeks after nonirradiation (n = 10), and LM8 implantation 12 weeks after 20-Gy irradiation (n = 10); female mice were used for a mammary tumor metastasis model and ddY mice, a closed-colony mice with genetic diversity, were selected to represent interhuman diversity. Mice in each group underwent surgery to generate a tumor-induced spinal cord compression model at either 6 weeks or 12 weeks after irradiation to assess changes in the meningeal barrier's ability to protect against tumor infiltration. During surgery, the mice were implanted with MMT (representative of a carcinoma) or LM8 tumor. When the mice became paraplegic because of spinal cord compression by the growing implanted tumor, they were euthanized and evaluated histologically. Four mice died from anesthesia and 10 mice per group were euthanized (MMT-implanted groups: MMT implantation occurred 6 weeks after nonirradiation [n = 10], 6 weeks after irradiation [n = 10], 12 weeks after nonirradiation [n = 10], and 12 weeks after irradiation [n = 10]; LM8-implanted groups: LM8 implantation performed 6 weeks after nonirradiation [n = 10], 6 weeks after irradiation [n = 10], 12 weeks after nonirradiation [n = 10], and 12 weeks after irradiation [n = 10]); 80 mice were evaluated. The spines of the euthanized mice were harvested; hematoxylin and eosin staining and Masson's trichrome staining slides were prepared for histologic assessment of each specimen. In the histologic assessment, intradural invasion of the implanted tumor was graded in each group by three observers blinded to the type of tumor, presence of irradiation, and the timing of the surgery. Grade 0 was defined as no intradural invasion with intact dura mater, Grade 1 was defined as intradural invasion with linear dural continuity, and Grade 2 was defined as intradural invasion with disruption of the dural continuity. Additionally, we euthanized 12 mice for a microstructural analysis of dura mater changes by two observers blinded to the presence of irradiation. Six mice (three mice in the 12 weeks after nonirradiation group and three mice in the 12 weeks after 20-Gy irradiation group) were quantitatively analyzed for defects on the dural surface with SEM. The other six mice (three mice in the 12 weeks after nonirradiation group and three mice in the 12 weeks after 20-Gy irradiation group) were analyzed for layer structure of collagen fibers constituting dura mater by TEM. In the SEM assessment, the number and size of defects on the dural surface on images (200 µm × 300 µm) at low magnification (× 2680) were evaluated. A total of 12 images (two per mouse) were evaluated for this assessment. The days from surgery to paraplegia were compared between each of the tumor groups using the Kruskal-Wallis test. The scores of intradural tumor invasion grades and the number of defects on dural surface per SEM image were compared between irradiation group and nonirradiation group using the Mann-Whitney U test. Interobserver reliabilities of assessing intradural tumor invasion grades and the number of dural defects on the dural surface were analyzed using Fleiss'κ coefficient. P values < 0.05 were considered statistically significant. RESULTS: There was no difference in the median (range) time to paraplegia among the MMT implantation 6 weeks after nonirradiation group, the 6 weeks after irradiation group, the 12 weeks after nonirradiation group, and the 12 weeks after irradiation group (16 days [14 to 17] versus 14 days [12 to 18] versus 16 days [14 to 17] versus 14 days [12 to 15]; χ2 = 4.7; p = 0.19). There was also no difference in the intradural invasion score between the MMT implantation 6 weeks after irradiation group and the 6 weeks after nonirradiation group (8 of 10 Grade 0 and 2 of 10 Grade 1 versus 10 of 10 Grade 0; p = 0.17). On the other hand, there was a higher intradural invasion score in the MMT implantation 12 weeks after irradiation group than the 12 weeks after nonirradiation group (5 of 10 Grade 0, 3 of 10 Grade 1 and 2 of 10 Grade 2 versus 10 of 10 Grade 0; p = 0.02). Interobserver reliability of assessing intradural tumor invasion grades in the MMT-implanted group was 0.94. There was no difference in the median (range) time to paraplegia among in the LM8 implantation 6 weeks after nonirradiation group, the 6 weeks after irradiation group, the 12 weeks after nonirradiation group, and the 12 weeks after irradiation group (12 days [9 to 13] versus 10 days [8 to 13] versus 11 days [8 to 13] versus 9 days [6 to 12]; χ2 = 2.4; p = 0.50). There was also no difference in the intradural invasion score between the LM8 implantation 6 weeks after irradiation group and the 6 weeks after nonirradiation group (7 of 10 Grade 0, 1 of 10 Grade 1 and 2 of 10 Grade 2 versus 8 of 10 Grade 0 and 2 of 10 Grade 1; p = 0.51), whereas there was a higher intradural invasion score in the LM8 implantation 12 weeks after irradiation group than the 12 weeks after nonirradiation group (3 of 10 Grade 0, 3 of 10 Grade 1 and 4 of 10 Grade 2 versus 8 of 10 Grade 0 and 2 of 10 Grade 1; p = 0.04). Interobserver reliability of assessing intradural tumor invasion grades in the LM8-implanted group was 0.93. In the microstructural analysis of the dura mater using SEM, irradiated mice had small defects on the dural surface at low magnification and degeneration of collagen fibers at high magnification. The median (range) number of defects on the dural surface per image in the irradiated mice was larger than that of nonirradiated mice (2 [1 to 3] versus 0; difference of medians, 2/image; p = 0.002) and the median size of defects was 60 µm (30 to 80). Interobserver reliability of assessing number of defects on the dural surface was 1.00. TEM revealed that nonirradiated mice demonstrated well-organized, multilayer structures, while irradiated mice demonstrated irregularly layered structures at low magnification. At high magnification, well-ordered cross-sections of collagen fibers were observed in the nonirradiated mice. However, disordered alignment of collagen fibers was observed in irradiated mice. CONCLUSION: Intradural tumor invasion and disruptions of the dural microstructure were observed in the meninges of mice after irradiation, indicating radiation-induced disruption of the meningeal barrier. CLINICAL RELEVANCE: We conclude that in this form of delivery, radiation is associated with disruption of the dural meningeal barrier, indicating a need to consider methods to avoid or limit Postradiation tumor relapse and spinal cord compression when treating spinal metastases so that patients do not experience intradural tumor invasion. Surgeons should be aware of the potential for intradural tumor invasion when they perform post-irradiation spinal surgery to minimize the risks for intraoperative dural injury and spinal cord injury. Further research in patients with irradiated spinal metastases is necessary to confirm that the same findings are observed in humans and to seek irradiation methods that prevent or minimize the disruption of meningeal barrier function.

Risk factors for skeletal-related events in patients with bone metastasis from breast cancer undergoing treatment with zoledronate.

BACKGROUND: Skeletal-related events (SREs) are significant contributors to the morbidity and mortality in patients with bone metastasis from breast cancer. Thus, bone-modifying agents (BMAs) are recommended in this population. However, the baseline risk factors of SREs in patients with bone metastasis from breast cancer receiving BMAs are not well understood. METHODS: We analyzed the patient-level data from a controlled arm of a clinical trial comparing denosumab with zoledronate in patients with bone metastases from breast cancer (ClinicalTrial.gov ID: NCT00321464) available at Project Data Sphere, a broad-access research platform that collects and curates patient-level data from completed, phase III cancer trials. The primary endpoint was the first SRE after the inclusion to the trial. The time to the first on study SRE was analyzed using Cox proportional hazards model based on patients' baseline characteristics including age, race, ECOG performance status (PS), histology and immunohistochemistry of breast cancer, and urine and serum laboratory data. RESULTS: Among 756 patients in the zoledronate arm of the trial, we excluded 64 patients with a documented history of osteopenia or osteoporosis. The median age of the patients was 56 years old, the median follow-up was 553 days, and 249 patients (36%) had SREs. The univariate analysis showed that black or African American heritage, ECOG PS > 0, human epidermal growth factor receptor 2 (HER2) positivity, high urine N-telopeptide cross-links / creatinine ratio (NTx/Cre), and elevated serum alkaline phosphatase (ALP) are significant baseline risk factors for SREs. Patients with the characteristics of ECOG PS > 0, HER2 positivity, and elevated ALP also showed a significantly higher hazard ratio of SREs in multivariate analysis. CONCLUSIONS: We determined risk factors for SREs in patients with bone metastasis from breast cancer.

Radiotherapy combined with zoledronate can reduce skeletal-related events in renal cell carcinoma patients with bone metastasis.

BACKGROUND: Skeletal-related events (SRE) are common in patients with renal cell carcinoma (RCC) that includes bone metastasis. The purpose of this study was to clarify the effectiveness of zoledronate with and without sunitinib, combined with radiotherapy, for the treatment of bone metastasis from RCC. METHODS: We retrospectively analyzed 62 RCC patients with bone metastasis, who had been treated with radiotherapy at our institution. We divided the study cohort into two groups: patients treated with radiotherapy alone (RT; n = 27) and those treated with radiotherapy combined with zoledronate (RT + Z; n = 35). We investigated the overall survival and post-irradiation (PI)-SRE-free rate for each group, as well as the effect of sunitinib in the RT + Z treatment group. In addition, we determined treatment effectiveness by imaging assessments and relative response rates. RESULTS: There was no significant difference in the survival rates between the RT and RT + Z treatment groups (p = 0.11). However, the PI-SRE-free rate in the RT + Z group was significantly higher than that in the RT group (p = 0.02). The PI-SRE-free rate was significantly higher in patients who were treated with sunitinib after radiotherapy than in those who were treated without sunitinib (p = 0.03). However, there was no significant difference in the relative response rates, as assessed by imaging, in each group. CONCLUSION: Radiotherapy combined with zoledronate is an effective treatment for RCC with bone metastasis to prevent PI-SRE. Sunitinib may reduce PI-SRE if used after radiotherapy and combined with zoledronate.

Approaches to radiotherapy in metastatic spinal cord compression.

Metastatic spinal cord compression is caused by the progression of metastatic lesions within the vicinity of the spinal cord. The consequences are very severe with loss of neurological function and severe pain. The standard treatment is surgical intervention followed by radiotherapy or radiotherapy alone. However, the majority of patients are treated with radiotherapy only due to contraindications to surgery and technical inoperability. Stereotactic body radiotherapy is a technology to deliver higher radiation dose to the radiotherapy target with the use of spatial coordinates. This modality has shown positive results in treating lesions in brain and lungs. Hence, it could prove beneficial in metastatic spinal cord compression. We designed and planned a trial to investigate this method in patients with metastatic spinal cord compression. The method was usable but the trial was stopped prematurely due to low accrual that made comparison with surgery impossible. Low accrual is a known problem for trials evaluating new approaches in radiotherapy. Target definition in radiotherapy of metastatic spinal cord compression is defined by patient history, examination and imaging. Functional imaging could provide information to guide target definition with the sparring of normal tissue e.g. spinal cord and hematopoietic tissue of the bone marrow. In future trials this may be used for dose escalation of spinal metastases. The trial showed that PET/MRI was feasible in this group of patients but did not change the radiotherapy target in the included patients. Neurological outcome is similar irrespective of course length and therefore single fraction radiotherapy is recommended for the majority of patients. In-field recurrence is a risk factor of both short and long fractionation schemes and re-irradiation have the potential risk of radiation-induced myelopathy. In a retrospective study of re-irradiation, we investigated the incidence of radiation-induced myelopathy. In our study population, we found a higher number of patients experiencing vertebral fractures than the number of patient developing myelopathy. Patients with diabetes had an increased risk of toxicity compared to the remaining patients. Stereotactic body radiotherapy is effective in treating metastatic spinal cord compression but the efficacy cannot be determined due low accrual. The use of PET/MRI did not spare normal tissue in radiotherapy planning of spinal metastases. The incidence of toxicity after re-irradiation of the spine and spinal cord was low. For patients with in-field recurrence, re-irradiation is safe and has a low incidence of toxicity.

Denosumab versus zoledronic acid in bone disease treatment of newly diagnosed multiple myeloma: an international, double-blind, double-dummy, randomised, controlled, phase 3 study.

BACKGROUND: Multiple myeloma is characterised by monoclonal paraprotein production and osteolytic lesions, commonly leading to skeletal-related events (spinal cord compression, pathological fracture, or surgery or radiotherapy to affected bone). Denosumab, a monoclonal antibody targeting RANKL, reduces skeletal-related events associated with bone lesions or metastases in patients with advanced solid tumours. This study aimed to assess the efficacy and safety of denosumab compared with zoledronic acid for the prevention of skeletal-related events in patients with newly diagnosed multiple myeloma. METHODS: In this international, double-blind, double-dummy, randomised, active-controlled, phase 3 study, patients in 259 centres and 29 countries aged 18 years or older with symptomatic newly diagnosed multiple myeloma who had at least one documented lytic bone lesion were randomly assigned (1:1; centrally, by interactive voice response system using a fixed stratified permuted block randomisation list with a block size of four) to subcutaneous denosumab 120 mg plus intravenous placebo every 4 weeks or intravenous zoledronic acid 4 mg plus subcutaneous placebo every 4 weeks (both groups also received investigators' choice of first-line antimyeloma therapy). Stratification was by intent to undergo autologous transplantation, antimyeloma therapy, International Staging System stage, previous skeletal-related events, and region. The clinical study team and patients were masked to treatment assignments. The primary endpoint was non-inferiority of denosumab to zoledronic acid with respect to time to first skeletal-related event in the full analysis set (all randomly assigned patients). All safety endpoints were analysed in the safety analysis set, which includes all randomly assigned patients who received at least one dose of active study drug. This study is registered with ClinicalTrials.gov, number NCT01345019. FINDINGS: From May 17, 2012, to March 29, 2016, we enrolled 1718 patients and randomly assigned 859 to each treatment group. The study met the primary endpoint; denosumab was non-inferior to zoledronic acid for time to first skeletal-related event (hazard ratio 0·98, 95% CI 0·85-1·14; pnon-inferiority=0·010). 1702 patients received at least one dose of the investigational drug and were included in the safety analysis (850 patients receiving denosumab and 852 receiving zoledronic acid). The most common grade 3 or worse treatment-emergent adverse events for denosumab and zoledronic acid were neutropenia (126 [15%] vs 125 [15%]), thrombocytopenia (120 [14%] vs 103 [12%]), anaemia (100 [12%] vs 85 [10%]), febrile neutropenia (96 [11%] vs 87 [10%]), and pneumonia (65 [8%] vs 70 [8%]). Renal toxicity was reported in 85 (10%) patients in the denosumab group versus 146 (17%) in the zoledronic acid group; hypocalcaemia adverse events were reported in 144 (17%) versus 106 (12%). Incidence of osteonecrosis of the jaw was not significantly different between the denosumab and zoledronic acid groups (35 [4%] vs 24 [3%]; p=0·147). The most common serious adverse event for both treatment groups was pneumonia (71 [8%] vs 69 [8%]). One patient in the zoledronic acid group died of cardiac arrest that was deemed treatment-related. INTERPRETATION: In patients with newly diagnosed multiple myeloma, denosumab was non-inferior to zoledronic acid for time to skeletal-related events. The results from this study suggest denosumab could be an additional option for the standard of care for patients with multiple myeloma with bone disease. FUNDING: Amgen.

Therapeutic approaches for protecting bone health in patients with breast cancer.

Improvements in the survival of patients with breast cancer, together with a better understanding of the pathology of the disease, have led to the emergence of bone health as a key aspect of patient management. Patients with breast cancer are typically at risk of skeletal complications throughout their disease course. The receptor activator of nuclear factor κ B ligand (RANKL) inhibitor denosumab and bisphosphonates (e.g. zoledronic acid) are approved in Europe for the prevention of skeletal-related events (pathologic fracture, radiation or surgery to bone, and spinal cord compression) in adults with bone metastases secondary to solid tumours. These agents are also approved at lower doses for the treatment of patients with postmenopausal osteoporosis, a population largely overlapping with those in the early stages of breast cancer, and those with cancer treatment-induced bone loss, which is caused primarily by aromatase inhibitors. In this review, we consider the evidence supporting the use of therapeutic agents to protect bone health throughout the course of breast cancer. Timing of treatment initiation, dose and treatment duration may prove to be barriers to the optimization of the practical use of these agents in the management of patients with breast cancer. Furthermore, with longer survival times, patients may expect to receive long-term treatment with denosumab or bisphosphonates, therefore consideration must be given to safety. Thus, we aim to summarize the recommendations for the use of these agents in management of patients with breast cancer in Europe. We also discuss the recent evidence for their potential antineoplastic effects.

Update on traumatic acute spinal cord injury. Part 2. / Actualización en lesión medular aguda postraumática. Parte 2.

The aim of treatment in acute traumatic spinal cord injury is to preserve residual neurologic function, avoid secondary injury, and restore spinal alignment and stability. In this second part of the review, we describe the management of spinal cord injury focusing on issues related to short-term respiratory management, where the preservation of diaphragmatic function is a priority, with prediction of the duration of mechanical ventilation and the need for tracheostomy. Surgical assessment of spinal injuries based on updated criteria is discussed, taking into account that although the type of intervention depends on the surgical team, nowadays treatment should afford early spinal decompression and stabilization. Within a comprehensive strategy in spinal cord injury, it is essential to identify and properly treat patient anxiety and pain associated to spinal cord injury, as well as to prevent and ensure the early diagnosis of complications secondary to spinal cord injury (thromboembolic disease, gastrointestinal and urinary disorders, pressure ulcers).

Meta-analysis comparing denosumab and zoledronic acid for treatment of bone metastases in patients with advanced solid tumours.

The purpose of this meta-analysis was to evaluate the efficacy of denosumab, compared with zoledronic acid (ZA), in delaying skeletal-related events (SREs) and enhancing overall survival in patients with advanced solid tumours and bone metastases. A systematic literature search of several electronic databases, including PubMed, Medline, Embase, the Cochrane Library, CKNI and Web of Science with Conference Proceedings, was performed. Only randomised controlled trials assessing denosumab in comparison with ZA, in patients with advanced solid tumours and metastatic-stage disease, were included. The primary outcome was the time to first SRE. The risk of developing subsequent on-study SREs and overall survival were also evaluated. Three randomised controlled trials with a total of 5,544 patients with advanced solid tumours and bone metastases were included in the meta-analysis. There were 2,776 patients treated with denosumab and 2,768 treated with ZA. The pooled analysis showed that denosumab was superior to ZA in delaying time to first on-study SRE (odds ratio [OR]: 0.82; 95% CI: 0.75-0.89, p < 0.0001) and multiple SREs (risk ratio: 0.81; 95% CI: 0.74-0.88, p < 0.0001). However, no significant difference was found in overall survival improvement between denosumab and ZA (OR: 1.02; 95% CI: 0.91-1.15, p = 0.71). This meta-analysis indicates that denosumab is superior to ZA in delaying SREs for patients with bone metastases. No significant difference was observed between denosumab and ZA, regarding overall survival. We support denosumab as a potential novel treatment option for the management of bone metastases in advanced solid tumours.

Tract-Specific Diffusion Tensor Imaging in Cervical Spondylotic Myelopathy Before and After Decompressive Spinal Surgery: Preliminary Results.

PURPOSE: Diffusion tensor imaging (DTI) metrics of the cervical spinal cord in patients with cervical spondylotic myelopathy (CSM) were compared to those measured in healthy volunteers, using tract-specific region of interests (ROIs) across all cervical intervertebral disc levels. METHODS: Magnetic resonance (MR) imaging of the cervical spinal cord was performed in four patients with CSM and in five healthy volunteers on a 3-T MR scanner. Region-specific fractional anisotropy (FA) and mean diffusivity (MD) were calculated on axial imaging with ROI placement in the anterior, lateral, and posterior regions of the spinal cord. FA and MD were also calculated on sagittal acquisitions. Nonparametric statistical tests were used to compare controls and patients before and after surgery. RESULTS: FA values were significantly lower (p = 0.050) and MD values were significantly higher (p = 0.014) in CSM patients measured at level of maximal compression before surgery than in healthy controls in lateral and posterior ROIs, respectively. In posterior ROIs, MD values were significantly higher in patients before surgery compared to controls at all levels except C7-T1. CONCLUSION: Patients with CSM may demonstrate region-specific changes in DTI metrics when compared to healthy controls. Changes in DTI metrics may also occur at levels remote from site of compression.

Cervical Osteochondroma Causing Myelopathy in Adults: Management Considerations and Literature Review.

BACKGROUND: Osteochondromas are the most frequent benign bone tumors but only rarely occur along the spinal column and even more rarely induce symptoms from spinal cord compression. CASE DESCRIPTIONS: We report 2 adult patients, both with a history of hereditary multiple exostoses, who presented with cervical myelopathy secondary to osteochondromas. The first patient is a 22-year-old man with numbness and weakness of his right upper limb and neck pain. Radiologic images showed a bony tumor arising from the C3 lamina with evidence of severe spinal cord compression. The second patient is a 20-year-old woman with weakness of her left upper and lower limbs and progressive numbness of the left hand, as well as neck and back pain. Radiologic images showed a bony tumor arising from the C4 lamina with evidence of significant spinal cord compression and cord signal abnormality. Both patients underwent surgical excision of the epidural mass and pathology confirmed a diagnosis of osteochondroma. CONCLUSIONS: We discuss the role of surgical intervention, management, and postoperative follow-up in adult patients with cervical osteochondromas. Recommended management includes radiographic imaging and surgical intervention, particularly when evidence of spinal cord impingement occurs. Consistent postoperative follow-up is necessary to ensure appropriate recovery of neurologic function. Surgical management of cervical osteochondromas typically results in excellent and stable clinical outcomes with rare recurrence.

Bone-targeted therapy use in patients with bone metastases from lung cancer: A systematic review of randomized controlled trials.

BACKGROUND: Patients with advanced lung cancer commonly have bone metastases. Compared with other malignancies, the use of bone-targeted agents (e.g. bisphosphonates and denosumab) is less common in lung cancer patients. This may be due to the perception that bone-targeted agents are less effective in this population. OBJECTIVE: To perform a systematic review to evaluate data from randomized trials of bone-targeted agents in lung cancer patients with bone metastases. METHODS: A systematic search of Medline, Embase and the Cochrane Register of Controlled Trials through May 2015 was performed. Randomized trials of bone-targeted therapies in lung cancer patients with bone metastases were sought. Outcomes studied included skeletal related events (SREs), pain, quality of life, progression-free survival and overall survival. Random effects meta-analyses were planned if studies were judged homogeneous. RESULTS: Of 632 abstracts, 17 publications describing 13 studies were included. Sample sizes ranged between 50 and 1776. Of 3379 patients, 1903 had lung cancer, with subgroup data available for 8 of 13 studies. Patient demographics were comparable, but enrollment criteria and endpoints were heterogeneous across studies, precluding meta-analysis. Study-specific results suggested that bone-modifying agents reduce the incidence of SREs and bone pain in lung cancer patients. Three studies suggested a survival benefit. CONCLUSION: Data from included trials suggests benefit of bone-targeted agents in lung cancer for the prevention of SREs and bone pain. There is a trend toward improvement in overall survival and progression-free survival, although further research is needed. Impact on quality of life and key subgroups for benefit both require future research.

[Spinal epidural lipomatosis as a rare side effect in steroid-dependent Jo-1 antibody syndrome]. / Spinale epidurale Lipomatose als seltene Nebenwirkung bei steroidabhängigem Jo-1-Antikörper-Syndrom.

Spinal epidural lipomatosis (SEL) of the thoracic and lumbar spine is a rare entity, which leads to compression of the spinal canal. The exact pathogenesis is still unknown. It most commonly occurs in patients with long-term exogenous or endogenous glucocorticoid excess or morbid obesity but there are also idiopathic forms. The symptoms depend on the severity of the SEL and can manifest as clinically asymptomatic, non-specific back pain, radiculopathy up to spinal cord compression. The diagnosis is usually achieved by magnetic resonance imaging (MRI) of the affected spinal segments. The treatment varies between discontinuation of glucocorticoids, weight reduction up to multisegmental decompressive laminectomy. The following case report presents the findings of SEL in a patient with steroid-dependent Jo-1 antibody syndrome and provides a current literature review on this rare disease.

Immediate Postoperative Reversal of Disc Herniation Following Facetal Distraction-Fixation Surgery: Report of 4 Cases.

BACKGROUND: We report cases of 4 patients where Goel facet distraction surgery resulted in restoration of herniated disc back into the intervertebral disc space in the immediate postoperative period. Such a fate of herniated disc has not been recorded earlier. METHODS: During the period 2010 to 2011, 4 patients with single level 'contained' herniated disc that extended to the posterior surface of adjoining vertebral bodies and resulted in severe cord and root compression were surgically treated. The posterior longitudinal ligament was essentially intact in all 4 cases. Surgery involved facetal distraction technique using Goel facet spacers as a standalone method of treatment. RESULTS: Immediate postoperative imaging showed nearly complete disappearance of the disc bulge, restoration of the cervical cord girth and distraction-fixation arthrodesis of the spinal segment. All patients had remarkable and sustained clinical improvement. At a 5-year follow-up, all 4 patients were well and showed no evidence of recurrent symptoms or recurrence of herniated disc-related imaging findings. CONCLUSIONS: The indications for facetal distraction surgery, its mechanisms of action and its suitability in the presented cases are discussed.

Epidural Venous Angioma Presenting with Spinal Cord Compression in a 42-Year-Old Woman with Previous History of Ovarian Malignancy.

BACKGROUND: Venous angioma is an extremely rare vascular malformation of the epidural space. To the best of our knowledge, only 5 cases have been documented to date and none has been reported in the setting of a previous malignancy. CASE DESCRIPTION: We report the case of a 42-year-old woman with a previous history of ovarian cancer, treated by surgery plus chemotherapy; who presented with signs of spinal cord compression for 3 weeks. Magnetic resonance imaging showed an intensely enhancing epidural mass at the T2-T6 level causing major spinal cord compression, for which urgent surgery was indicated. During surgery, the tumor was extremely hemorrhagic and the hemostasis was hazardous. Blood loss was estimated at 1.5 L, causing hemodynamic instability and requiring intensive resuscitation with fluids and blood transfusions. Gross total resection was achieved and the pathologic examination confirmed the diagnosis of venous angioma. The patient recovered quickly postoperatively and was able to walk independently within 2 weeks of starting intensive rehabilitation. She was symptom free with no clinical or radiologic evidence of recurrence at 1 year follow-up. CONCLUSIONS: Venous angioma should be included in the differential diagnosis of spinal epidural masses even in case of previous malignancy. Subtle imaging features should alert clinicians to this rare yet potentially life-threatening condition. Surgery remains the cornerstone of the treatment and can result in remarkable recovery.

[FGF23 related hypophosphatemic rickets:current therapy and unresolved issues].

FGF23-related hypophosphatemic rickets is basically treated with active vitamin D and phosphorus. The treatment goals are to minimize bone deformity and improve adult height in children, and to relieve pain and decrease osteomalacia in adult. However, since they do not target the underlying molecular defect, bone deformity can worsen during growth and adult height is suboptimal restricted. Many adult patients suffer from enthesopathy leading to symptoms such as spinal cord compression and debilitating pain. At present, no treatment is effective in preventing or revenging this complication. The recently developed anti-FGF23 antibody may potentially be a more fundamental treatment.