Spine Bone Research Articles

Langerhans Cell Histiocytosis In Bone: A Case Report

Langerhans cell histiocytosis (LCH) is a rare disease in which histiocytic infiltrations can be seen in bone, skin, lymph nodes, lungs, liver, spleen, bone marrow, central nervous system and endocrine glands. Pulmonary LCH has been closely associated with smoking while there is no data on genetic, viral or neoplastic etiology. In LCH with multiple system involvement, unifocal/multifocal infiltrations occur in two or more organs together with systemic symptoms such as weight loss and fever. In histology, Langerhans cells that do not contain phagocytic material in their cytoplasm, have a folded "coffee bean" appearance in their nucleus, express histiocyte markers CD1a, S100 and C207 and contain Birbeck granules under electron microscope. In treatment, if there is a risk of collapse in spinal or femoral bone lesions, surgery and radiotherapy can be applied for stabilization; if necessary, chemotherapy can be applied in multisystem disease. Here, we reported a LCH patient with a malignant shaped lytic lesion in the thoracic spine and adjacent bone.

Simulated Galactic Cosmic Rays Modify Mitochondrial Metabolism in Osteoclasts, Increase Osteoclastogenesis and Cause Trabecular Bone Loss in Mice.

Space is a high-stress environment. One major risk factor for the astronauts when they leave the Earth’s magnetic field is exposure to ionizing radiation from galactic cosmic rays (GCR). Several adverse changes occur in mammalian anatomy and physiology in space, including bone loss. In this study, we assessed the effects of simplified GCR exposure on skeletal health in vivo. Three months following exposure to 0.5 Gy total body simulated GCR, blood, bone marrow and tissue were collected from 9 months old male mice. The key findings from our cell and tissue analysis are (1) GCR induced femoral trabecular bone loss in adult mice but had no effect on spinal trabecular bone. (2) GCR increased circulating osteoclast differentiation markers and osteoclast formation but did not alter new bone formation or osteoblast differentiation. (3) Steady-state levels of mitochondrial reactive oxygen species, mitochondrial and non-mitochondrial respiration were increased without any changes in mitochondrial mass in pre-osteoclasts after GCR exposure. (4) Alterations in substrate utilization following GCR exposure in pre-osteoclasts suggested a metabolic rewiring of mitochondria. Taken together, targeting radiation-mediated mitochondrial metabolic reprogramming of osteoclasts could be speculated as a viable therapeutic strategy for space travel induced bone loss.

Phase II Trial of SBRT and Androgen Deprivation for Oligometastases in Prostate Cancer

SBRT-SG 05 is a collaborative (SBRT-SG, GICOR and SEOR) prospective multicenter phase II trial testing SBRT and androgen deprivation therapy (ADT) in oligorecurrent prostate cancer patients.Prostate cancer patients (hormone-sensitive or castration-resistant) in an oligorecurrent stage defined as less than 5 bone or lymph node metastases by Choline PET-CT or/and WB-DWI-MRI, after primary treatment, were assigned to receive ADT and SBRT (Vertebral metastases: 1 × 16-18Gy or 3 × 8-9Gy; lymph node metastases: 3 × 10-11 Gy or 6 × 7,5Gy; non-spinal bone metastases: 1 × 16Gy or 3 × 10Gy). Inclusion criteria included: more than 1 year from primary treatment to biochemical recurrence and PSA doubling time greater than 2 months. A minimum of 24 months of LhRh analogues from the time of the enrollment was required and concomitant treatment with chemotherapy, abiraterone or enzalutamide was not allowed. Oncologic outcomes defined by PCWG3 were evaluated separately for hormone-sensitive and castration-resistant patients, using Kaplan-Meier competing risks, and Cox regression. Toxicity was prospectively evaluated according to CTCAE.v4 criteria.From 07/2014 to 12/2019, 81 patients from 14 Spanish centers were recruited with a total of 117 oligometastases treated, 67 in lymph nodes, 43 in non--spinal bones and 7 in spinal bones. 14 patients were recruited in a castration-resistance status. Median follow-up was 41 months, (range 18 - 72 months). 13 hormone-sensitive (19,4%) and 8 castration-resistant (57,1%) oligorecurrent patients presented distant disease progression. Median distant progression-free survival (DPFS) was 54,2 months (IC95% = 48,2 - 60,3). 18 of the patients who progressed (85,7%) were treated with SBRT for the new lesions, 7 of them presented a subsequent distant progression (38,9%), with a median of second DPFS of 24,4 months (95% CI = 23,7 - 25,2). In the castration resistant subgroup, median DPFS was 33,5 months (range 14,8 - 52,1), 42,9% of them were free from distant disease progression at last follow-up, without the need to start second generation hormonal treatment. Tolerance and toxicity profiles were excellent, none of the patients developed toxicity ≥G3 or symptoms related to local progression of the disease.Combination of SBRT and ADT is a safe treatment approach with favorable clinical outcomes for hormone-sensitive and castration-resistant prostate cancer patients. Validation studies are needed in castration-resistant patients. ClinicalTrials.gov Identifier: NCT02192788.

Stereotactic Body Radiation Therapy for the First-Line Comprehensive Treatment of Oligometastatic Nasopharyngeal Carcinoma: A Prospective, Single-Arm, Phase II Trial

The current treatment strategy for patients with metastatic nasopharyngeal carcinoma (NPC) is mainly based on palliative chemotherapy, with low complete remission rate and poor progression-free survival (PFS). Radiation therapy has proven efficacy in the treatment of patients with nonmetastatic NPC, with emerging indication in the setting of limited metastatic disease. We proposed a single-arm phase II study to determine if metastasis-directed SBRT plus systemic treatment could prolong PFS compared with historical findings at first-line therapy for patients with oligometastatic NPC.We enrolled metastatic NPC with 1-5 metastatic lesions, with all metastases amenable to SBRT. Prescribed doses ranged from 25-50 Gy administered in five fractions. All patients received systemic chemotherapy before or after SBRT. The primary endpoint was PFS at 1 year from the start of SBRT treatment.Between October 2016 and January 2020, 24 patients with a median age of 48 years (range, 29-65 years) were recruited. A total of 44 sites were treated with 11 of 24 patients receiving SBRT to more than one site. Spinal bone was most often irradiated. By Kaplan-Meier actuarial analysis, 1-year PFS was 62% and overall survival rate 87%. Most patients progressed in new distant sites with only one local SBRT failures out of 44 lesions. Patients with lung metastasis had a lower chance of distant progression than those with bone metastasis or liver metastasis. There were no SBRT relevant grade 3-5 toxicity, and only one patient suffered from grade 2 adverse event.Use of metastasis-directed SBRT with systemic chemotherapy for patients with oligometastatic NPC as first-line therapy was well tolerated, and resulted in high PFS, substantially greater than historical values for patients who only received systemic agents.

Changes of Bone Strength Evaluated by CT-based Finite Element Methods in Radiotherapy for Bone Metastases of the Spine in Comparison With Bone Density

Radiotherapy (RT) is performed not only to reduce pain but also to prevent pathological fractures due to bone metastases of the spine. However, it is unclear to what extent radiotherapy increases bone strength. Bone density is sometimes used as a marker for assessment of local response to RT in spinal bone metastases. The purpose of this study was to evaluate the changes of bone strength using CT-based finite element (FE) methods in radiotherapy for metastases at the lumber vertebra in comparison with bone density.Five patients with metastases to the lumber vertebra who could be followed for more than 6 months were included. Primary lesions were lung cancer in all patients. All patients had osteolytic changes of the bone cortex in the vertebral body. Median radiation dose was 37.8 Gy in 14 fractions. CT images were taken before and at 1, 3, 6, 9 and 12 months after irradiation. Bone density was measured in Hounsfield units (HU) in each CT scan. The regions of interest were set to include the whole vertebral body of the metastatic spine and that of a non-irradiated unaffected neighboring spine used for reference. The 3-dimensional FE models of the same vertebrae were constructed from each CT image. The models consisted of 1- or 2-mm linear tetrahedral elements and the cortical shell with a thickness of 0.1 mm. A uniaxial compressive load with uniform distribution was applied on the upper surface of the vertebral body with the lower surface completely restrained. The predicted fracture load was defined to be present when at least one element or cortical shell failed. The ratios of the values on the follow-up CT to the values on the pre-irradiation CT were calculated, and single regression equations were determined for these ratios.At one month after irradiation, the bone density decreased in all except one case of the affected vertebral bodies, and the predicted fracture load decreased in all except one case of the unaffected vertebral bodies. In the affected vertebral bodies, the slopes of the single regression equations of bone density were positive in 4 out of 5 cases. The slopes of those of predicted fracture loads were negative in 3 out of that 4 cases. In the unaffected vertebral bodies, the slopes of the single regression equations of bone density were positive in 3 out of 5 cases. The slopes of predicted fracture loads were positive in those 3 cases.The bone strength might not improve in one month after irradiation. The predicted fracture load did not necessarily increase even if the bone density increased in the irradiated affected vertebral bodies. Bone density alone might not be sufficient as an indicator of bone strength. The FE method could evaluate the changes in bone strength in radiotherapy for bone metastases based on predicted fracture loads.

Comparative Analyses of Two Established Scores to Assess the Stability of Spinal Bone Metastases Before and After Palliative Radiotherapy.

Background and PurposeTo compare two validated spinal instability scores regarding the stabilizing effects and skeletal-related events (SREs) of palliative radiotherapy (RT) in patients with spinal bone metastases (SBM).Materials and MethodsTwo hundred eighty-two osteolytic SBM of lung or breast cancer patients were analyzed for stability before and following RT based on the Spinal Instability Neoplastic Score (SINS) or the Taneichi score. Score concordance was quantified by absolute agreement and Cohen’s kappa coefficient. SREs were defined as fractures or local progression after RT. OS was quantified as the time between the start of RT and death from any cause.ResultsAt 3 and 6 months after RT, 35 and 50% of initially unstable SBM were re-stabilized according to SINS in patients still alive. Corresponding Taneichi score-based stabilization proportions were 25 and 46%, respectively. Comparison of both stability scores showed high absolute agreement for all time-points (range 71–78%, kappa range 0.35–0.44). SRE occurred more frequently in initially unstable SBM compared to stable SBM according to SINS (14 vs. 5%), but no such association could be shown for the Taneichi-based instability criterion. Poor general condition of patients was negatively associated with SINS-measured re-stabilization after 6 months, but no predictive factor for re-stabilization could be found for the Taneichi score.ConclusionsDespite the relatively high agreement between both stabilization scores, the SINS should be considered the standard for future studies on the stabilization effects of RT in SBM.

P24 Ankylosing spondylitis & uveitis - challenges in management

Case report - IntroductionAnkylosing spondylitis is a chronic inflammatory condition involving spine, chest and sacroiliac joints. It can be associated with extra spinal manifestations which include uveitis and enthesitis, as well as other features of an inflammatory spondyloarthropathy including psoriasis and inflammatory bowel disease. It is characterised by the presence of inflammatory back pain, limited range of spinal movement, sacroiliitis on imaging, excess spinal bone formation and a high prevalence of HLA-B27. The main aims of treatment are to improve symptoms and retain function as well as to prevent disease complications.Case report - Case descriptionA 49-year-old male diagnosed with ankylosing spondylitis at the age of 23 (HLA-B27 positive, classical radiographic features on plain radiographs and MRI), with background of meningitis and subsequent epilepsy (not on treatment since the age of 13), severe hip osteoarthritis and osteoporosis. He has peripheral elbow and knee synovitis. At the age of 27 he developed sight-threatening bilateral recurrent anterior uveitis complicated by cystoid macular oedema (causing central vision loss). Initial management included anti-inflammatories and steroids. He progressed to biologics but developed a rash on adalimumab. He was switched to infliximab in 2010. In 2015 it was switched due to reduced response to golimumab which was non-beneficial. Subsequently he was switched to etanercept but after 3 months it was discontinued due to eye flare. The patient’s therapy was switched to certolizumab, which was non-beneficial for spine and discontinued. In 2016, infliximab was retried as the patient thought it worked best. Unfortunately, in 2018 patient developed Infliximab antibodies and treatment was changed to secukinumab. After 9 months this was stopped owing to ongoing active eye and spine disease. Adalimumab was re-tried; however, it was discontinued as it was showing no benefit. In 2020 Eeanercept (Benepali) was re-tried; however, only for 4 months because of severe flare of joint and eye disease. Tofacitinib was commenced but was non-beneficial and hence it was discontinued. Currently he continues on ixekizumab, oral prednisolone and also receives steroid eye and joint injections. On commencing biologics he was on methotrexate; however, the patient stopped. He was switched to mycophenolate mofetil which he remained on for 10 years. It was switched to methotrexate to try and control peripheral inflammatory joint disease better (re-tried for the second time) which the patient has recently discontinued as he felt it was non-beneficial.Case report - DiscussionThe case is very challenging. The patient’s disease continues to flare despite changing therapies. He continues to get flares in his back disease, eye disease and peripheral synovitis. His latest BASDI was 5.1 and VAS was 9/10. Measurements: intermalleolar distance 15cm, modified Schober’s 4cm, right lateral flexion 3.8cm and left lateral flexion 11cm. His latest MRI of whole spine and SI joints (in 2020) showed signs of previously active seronegative spondyloarthropathy with established cervical and thoracic ankyloses as well as bilateral sacroiliac joint ankylosis. There is a need for repeated steroid injections to the knees as well as the eyes. He continues on oral prednisolone which was first started in 2006. This is associated with multiple side effects, i.e., osteoporosis. The patient has already completed 8 years of bisphosphonate therapy. He is under regular review with the osteoporosis clinic. His bone density scan showed worsening bone mineral density and bisphosphonates had to be restarted. The patient adjusted medications depending on his symptoms. Recently he also discontinued methotrexate as he felt it was of no benefit to him at all. We are very limited at present to find combined medications to manage both the patient’s inflammatory back disease and inflammatory eye disease.Case report - Key learning pointsThis patient was diagnosed with ankylosing spondylitis 26 years ago. To date he has tried 5 different anti-TNF agents (two of which have also been re-tried at a different time point). This failed to control his disease as he continued to experience flares in either inflammatory back or eye disease. The biologic classes were also changed – he has tried one IL-17A agent as well as a JAK-I. Unfortunately, they both failed to control his disease. He currently continues on a second IL-17A; however, he still requires steroid eye and joint injections as well as systemic steroids. Throughout the years he has tried different DMARDs – most recently methotrexate. Unfortunately, the patient decided to discontinue it as he felt it was of no benefit to him. All of the above indicates that there is still a need to find a collaborative treatment option that will control the patient’s inflammatory back disease, inflammatory eye disease and peripheral synovitis. The aim would be, if possible, to decrease the steroid dose as well (currently on prednisolone 15mg daily) in order to prevent the steroid-associated side effects.

Assessment of bone quality with trabecular bone score in patients with inflammatory bowel disease

Inflammatory bowel disease (IBD) patients have a significant risk of developing bone loss. The trabecular bone score (TBS) is a relatively new parameter used to provide information on bone quality. The study cohort included 81 patients with IBD and 81 healthy controls. Blood tests, dual-energy x-ray absorptiometry (DXA), including TBS, were assessed. Harvey–Bradshaw Index (HBI) for Crohn's disease (CD) and the Partial Mayo Score for ulcerative colitis (UC) were used for evaluation of clinical disease activity. Compared with the healthy controls, the IBD patients had lower lumbar spine (LS) bone mineral density (BMD) (1.06 ± 0.18 vs. 1.16 ± 0.15 g/cm2, p < 0.005), hip BMD (0.88 ± 0.13 vs. 0.97 ± 0.13 g/cm2, p < 0.005) and TBS (1.38 ± 0.1 vs. 1.43 ± 0.1, p < 0.005) values. The patients with stricturing CD had lower TBS (1.32 ± 0.13 vs. 1.40 ± 0.9, p = 0.03) and LS BMD (0.92 ± 0.19 vs. 1.07 ± 0.1, p = 0.01) values compared with those with non-stricturing CD. Multivariate regression model analysis identified HBI as independent factor associated with TBS. Our results support that all DXA parameters are lower in patients with IBD than in healthy patients. Moreover, TBS is a valuable tool for assessment of bone impairment in active CD.

Bipolar Radiofrequency Ablation of Painful Spinal Bone Metastases Performed under Local Anesthesia: Feasibility Regarding Patient's Experience and Pain Outcome.

Background and objectives: To assess the pain relief of bipolar RFA combined or not with vertebroplasty in patients with painful vertebral metastases and to evaluate the feasibility and tolerance of the RFA procedure performed under local anesthesia. Materials and Methods: 25 patients (18 men, 7 women, mean age: 60.X y.o) with refractory painful vertebral metastasis were consecutively included between 2012 and 2019. A total of 29 radiofrequency ablation (RFA) procedures were performed under CT guidance, local anesthesia and nitrous oxide inhalation, including 16 procedures combined with vertebroplasty for bone consolidation purposes. Pain efficacy was clinically evaluated using the visual analogue scale (VAS) at day 1, 1 month, 3 months, 6 months and 12 months, and the tolerance of the procedure was evaluated. Results: Procedure tolerance was graded as either not painful or tolerable in 97% of cases. Follow-up postprocedure mean VAS score decrease was 74% at day 1: 6.6 (p < 0.001), 79% at 1 month: 6.6 (p < 0.001), 79% at 3 months: 6.5 (p < 0.001), 77% at 6 months, and 79% at 12 months: 6.6 (p < 0.001). Conclusions: Bipolar RFA, with or without combined vertebroplasty, appears to be an effective and reliable technique for the treatment of refractory vertebral metastases in patients in the palliative care setting. It is a feasible procedure under local anesthesia which is well tolerated by patients therefore allowing to broaden the indications of such procedures. Field of study: interventional radiology.

Skeletal-Related Events (SRE) in Prostate Cancer: A Report of Two Cases

A skeletal-related event (SRE) is an event occurring due to bone metastasis in prostate cancer. SREs are usually marked by pain, pathological fractures, spinal cord compression, hypercalcemia, or bone metastasis requiring radiotherapy or operation. Case I: A 64-year-old male was diagnosed with a pathological fracture of the left femur. Thoracal CT scan showed osteoblastic lesions in the thoracal vertebrae, sternum, clavicle, and humeral head. Spinal MRI showed destruction of the cervical to sacral vertebral bodies. The histopathological result with Adenocarcinoma Gleason scores 8 (4+4) and an initial prostate-specific antigen (PSA) level of 689,7 ng/dL. Afterward, subcapsular orchiectomy was performed. However, his PSA level was still high (&gt;100 ng/dL) even after serum testosterone had reached a castration level. The patient died during the first chemotherapy using docetaxel. Case II: A 61-year-old male was diagnosed with inferior paraplegia and neurogenic bladder, paraparesis, urinary retention, and pain in the flank area. Spinal MRI showed a pathological compression fracture of the 8th thoracic vertebrae. Thoracal CT scan showed costal and 8th thoracal vertebrae destruction as well as multiple nodules in the lungs. Histological results with Adenocarcinoma Gleason score 9 (4+5) and an initial PSA level of 750 ng/dL. Afterward, subcapsular orchiectomy was performed. Serum testosterone reached castration level with the lowest PSA concentration of 21.6 g/dL. The patient declined chemotherapy and agreed to palliative treatment. He died one year after diagnosis. A high PSA level (&gt;500 ng/dL) could potentially be used as a predictor for severe SRE.

The role of percutaneous transarterial embolization in the management of spinal bone tumors: a literature review.

Spinal bone tumors include a heterogeneous broad of primary or metastatic lesions that may present as incidental findings or manifest with painful symptoms and pathological fractures. Optimal management of spine bone lesions is often difficult and treatment algorithms are usually solidly based on surgery. We aimed to evaluate the contribution of trans-arterial embolization in this field, with particular attention to the procedure efficacy, technical difficulties and complications. We present a literature review on the role of trans-arterial embolization in the management of spinal bone tumors, both primary and metastatic, evaluating its contribution as preoperative treatment, palliative procedure and standalone curative strategy. Trans-arterial embolization provides an important contribution to reducing surgery hemorrhagic risks, offering a better visualization of the operating field, and possibly increasing tumor susceptibility to chemotherapy or radiation therapy. Nonetheless, it plays an important part in pain palliation, with the unquestionable advantage of being easily repeatable in case of necessity. Its curative role as a standalone therapy is still subject of debate, and at the present time, satisfactory results have been recorded only in the treatment of aneurysmal bone cysts. Percutaneous trans-arterial embolization has established as a highly useful minimally invasive procedure in the management of spinal bone lesions, particularly as adjuvant preoperative therapy and palliative treatment.

Minimally invasive colostomy with endoscopy as a novel technique for creation of a trephine stoma

The conventional approach of trephine stoma creation is associated with various limitations, including poor elevation of the sigmoid colon, misidentification of the target organs, and poor visualization of the operative field, which may require conversion to an open approach. Our study aimed to evaluate the safety, feasibility, and complications of minimally invasive colostomy with endoscopy (MICE), a new technique for trephine stoma creation. This retrospective cohort study included 14 patients. Patients diagnosed with obstructive rectal cancer or bladder and rectal disorders due to spinal cord injury or bone metastasis requiring sigmoid loop colostomy were eligible for the procedure. MICE was performed using a combination of endoscopic and fluoroscopic procedures. The primary endpoint was the technical success of MICE. Technical success using MICE was achieved in all 14 cases. The mean total operative time was 52.6 (range 32–107) min, and mean blood loss was 18.9 (range 1–50) mL. There was no incidence of conversion to open surgery. Postoperative complications included peristomal abscess formation and ischemic colitis in each case. MICE may be useful as a minimally invasive approach for trephine stoma creation that overcomes the problems of a conventional approach in high-risk patients.

Translation of a spinal bone cement product from bench to bedside

Spinal acrylic bone cements (ABCs) are used clinically for percutaneous vertebroplasty (PVP) and kyphoplasty (PKP) to treat osteoporotic vertebral compression fractures. Product translation of spinal ABC products followed the design control processes including design verification and validation. The bench to bedside translation of the first Chinese spinal ABC product (Alliment®, namely Alliment Cement) approved by National Medical Products Administration of China was investigated and another commercial product served as the control (Osteopal®V, namely Osteopal V Cement). Results of non-clinical bench performance verification tests of compression, bending and monomer release showed that the newly marketed Alliment Cement is similar to the Osteopal V Cement with properties of both meeting the criteria specified by standards. The Alliment Cement demonstrated good biocompatibility during the 26 weeks’ bone implantation test. Porcine cadaver validation tests further revealed that the Alliment Cement satisfied the needs for both PVP and PKP procedures. A post-approval, retrospective clinical investigation further demonstrated the safety and efficacy of the Alliment Cement, with a significant reduction of pain and the improved stability of the fractured vertebral bodies. A successful translation of biomaterial medical products needs close collaborations among academia, industry, healthcare professionals and regulatory agencies.

Pediatric Reference Centiles of Bone Mineral Density and Body Composition of Lower Limbs

Localized neurological diseases such as spina bifida are often accompanied by normal upper limb and spinal bone mineral density (BMD), whereas regional BMD of the lower limbs may be decreased. Therefore, regional BMD measurements may be more accurate to quantify regional bone health. Until now, no pediatric reference centiles of bone mineral density and body composition of the lower extremities are available for Hologic DXA systems. The objective was to generate age-and sex specific reference centiles of DXA scans of lower limbs for Hologic DXA systems. Data from the National Health and Nutrition Examination Survey of the period 1999–2004 (age 8 – 20 years) were used to generate age-specific and sex-specific reference centiles for the non-Hispanic Black, non-Hispanic White and Mexican-American NHANES study population. The LMS method was used to calculate the reference centiles. Data of DXA scans of 2233 non-Hispanic black children (880 females), 1869 non-Hispanic white children (803 females) and 2350 Mexican American children (925 females) were used to create age-specific and sex-specific reference curves. We presented age-and sex-specific reference centiles for regional bone mineral density, bone mineral content, lean body mass and fat mass at the lower limbs for children and adolescents which were ethnicity specific and directly applicable to Hologic QDR-4500A fan-beam densitometer.

Probiotics as a New Regulator for Bone Health: A Systematic Review and Meta-Analysis.

Despite the proposed role of the gut microbiota-bone axis, findings on the association between probiotic consumption and bone health are conflicting. This systematic review aimed to assess the effect of probiotic consumption on bone health parameters. A systematic literature search of relevant reports published in PubMed/Medline, Web of Science, SCOPUS, EMBASE, and Google scholar before December 2020 was conducted. All clinical trials or experimental studies, which examined the relationship between probiotic consumption and bone health parameters, were included. No limitation was applied during the search. After screening articles based on inclusion criteria, 44 studies remained. In clinical trials, probiotic consumption affects bone health parameters such as serum calcium levels (3.82; 95% CI: 1.05, 6.59 mmol/l), urinary calcium levels (4.85; 95% CI: 1.16, 8.53 mmol/l), and parathyroid hormone (PTH) levels (−5.53; 95% CI: −9.83, −0.86 ng/l). In most studies, Lactobacillus species such as L. helveticus, L. reuteri, and L. casei were consumed and women aged 50 years or older were assessed. Spinal and total hip bone mineral density (BMD) was not affected significantly by probiotic consumption. In 37 animal experiments, probiotic or symbiotic feeding mostly had effects on bone health parameters. Some strains of Bifidobacterium and Lactobacillus including L. reuteri, L. casei, L. paracasei, L. bulgaricus, and L. acidophilus have indicated beneficial effects on bone health parameters. In conclusion, this systematic review and meta-analysis indicate that probiotic supplementation might improve bone health. Further studies are needed to decide on the best probiotic species and appropriate dosages.

Dental Implant for Maxillary Cancellous Alveolar Bone with Expandable Transformation in Apical Part.

The focus of this study is to propose a new implant design that will resemble the tooth anatomy as with three roots thus increase the primary stability in bone and open new indications to dental implant applications. Developed implant design and control implants were fabricated from Grade 4 type medical titanium. Three different media are selected as similar structural mechanical properties of alveolar cancellous bone quality; bovine iliac bone, bovine spinal bone, and polymer block. Implant sites were prepared with a 2-mm final drill. Then implants were inserted and all insertion torques were recorded. Starting from 5 Ncm implants were applied removal torques to test the initial stability. The sample that withstands the removal torque is marked with "+" until the torque value where the implant started to move out from the bone socket. Different bone structures and polymer material, designed implant with apical arms have shown relatively average gains of % 38.6 in bovine spinal bone samples, % 38.2 in bovine iliac bone samples and % 46.4 gain in polymer block in retention to removal torques. In the Bovine spinal bone environment, the percentage of gain of the Implant Group developed was significantly higher than the Control Implant Group (p: 0.000; P < 0.05). In the Bovine iliac bone medium, the percentage of gain of the Implant Group developed was significantly higher than the Control Implant Group (p: 0.002; P < 0.05). In the Polymer block environment, the gain percentage of the Implant Group developed was significantly higher than the Control Implant Group (p: 0.008; P < 0.05). The results of this study indicate promising positive future directions to make further researches on the material production and testings of such a new dental implant design including in vivo clinical controlled studies will be beneficial for better understanding the behavior of the developed implant design under different conditions.

MRI-Based Radiomics Nomogram as a Potential Biomarker to Predict the EGFR Mutations in Exon 19 and 21 Based on Thoracic Spinal Metastases in Lung Adenocarcinoma

Preoperative identifications of epidermal growth factor receptor (EGFR) mutation subtypes based on the MRI image of spinal metastases are needed to provide individualized therapy, but has not been previously investigated. This study aims to develop and evaluate an MRI-based radiomics nomogram for differentiating the exon 19 and 21 in EGFR mutation from spinal bone metastases in patients with primary lung adenocarcinoma. A total of 76 patients underwent T1-weighted and T2-weighted fat-suppressed MRI scans were enrolled in this study, 38 were positive for EGFR mutation in exon 19 and 38 were in exon 21.MRI imaging features were extracted and selected from each MRI pulse sequence, and used to form the radiomics signature. A radiomics nomogram was developed integrating the radiomics signature and important clinical factors with receiver operating characteristic, calibration and decision curve analysis to assess the nomogram. Clinical characteristics were analyzed with Mann-Whitney U and Chi-Square tests to identify the most important factors. A total of 6 features were selected as the most discriminative predictors from the two MRI pulse sequences. The nomogram integrating the combined radiomics signature, age and CEA level generated good prediction performance in the training (AUCs, nomogram vs. combined radiomics signature vs. clinical model, 0.90 vs. 0.87 vs. 0.59) and validation (AUCs, nomogram vs. combined radiomics signature vs. clinical model, 0.88 vs. 0.86 vs. 0.72) cohort. DCA analysis confirmed the potential clinical utility of the nomogram. This study demonstrated that MRI features from spinal bone metastases can be used to prognosticate EGFR mutation subtypes in exon 19 and 21. The developed pre-treatment nomogram can potentially guide treatments for lung adenocarcinoma patients.

Ligand-Dependent and Ligand-Independent Effects of Ephrin-B2-EphB4 Signaling in Melanoma Metastatic Spine Disease.

Tumor–endothelial cell interactions represent an essential mechanism in spinal metastasis. Ephrin-B2–EphB4 communication induces tumor cell repulsion from the endothelium in metastatic melanoma, reducing spinal bone metastasis formation. To shed further light on the Ephrin-B2–EphB4 signaling mechanism, we researched the effects of pharmacological EphB4 receptor stimulation and inhibition in a ligand-dependent/independent context. We chose a preventative and a post-diagnostic therapeutic window. EphB4 stimulation during tumor cell seeding led to an increase in spinal metastatic loci and number of disseminated melanoma cells, as well as earlier locomotion deficits in the presence of endothelial Ephrin-B2. In the absence of endothelial Ephrin-B2, reduction of metastatic loci with a later manifestation of locomotion deficits occurred. Thus, EphB4 receptor stimulation affects metastatic dissemination depending on the presence/absence of endothelial Ephrin-B2. After the manifestation of solid metastasis, EphB4 kinase inhibition resulted in significantly earlier manifestation of locomotion deficits in the presence of the ligand. No post-diagnostic treatment effect was found in the absence of endothelial Ephrin-B2. For solid metastasis treatment, EphB4 kinase inhibition induced prometastatic effects in the presence of endothelial Ephrin-B2. In the absence of endothelial Ephrin-B2, both therapies showed no effect on the growth of solid metastasis.

Bone and Mineral Metabolism Phenotypes in MEN1-Related and Sporadic Primary Hyperparathyroidism, before and after Parathyroidectomy

Primary hyperparathyroidism (PHPT) is the most common endocrinopathy in multiple endocrine neoplasia type 1 (MEN1). Persistent levels of increased parathyroid hormone (PTH) result in a higher incidence of osteopenia and osteoporosis compared to the general population. Surgical removal of hyper-functioning parathyroid tissue is the therapy of choice. This retrospective study evaluated the effect of parathyroidectomy (PTX) on bone metabolism and bone mass in two series of patients with MEN1 PHPT and sporadic PHPT (sPHPT) by comparing bone metabolism-related biochemical markers and bone mineral density (BMD) before and after surgery. Our data confirmed, in a higher number of cases than in previously published studies, the efficacy of PTX, not only to rapidly restore normal levels of PTH and calcium, but also to normalize biochemical parameters of bone resorption and bone formation, and to improve spine and femur bone mass, in both MEN1 PHPT and sPHPT. Evaluation of single-patient BMD changes after surgery indicates an individual variable bone mass improvement in a great majority of MEN1 PHPT patients. In MEN1 patients, PTX is strongly suggested in the presence of increased PTH and hypercalcemia to prevent/reduce the early-onset bone mass loss and grant, in young patients, the achievement of the bone mass peak; routine monitoring of bone metabolism and bone mass should start from adolescence. Therapy with anti-fracture drugs is indicated in MEN1 patients with BMD lower than the age-matched normal values.

Off-Label Use of Teriparatide in Spine.

Teriparatide belongs to osteo-anabolic compounds and has been used in recent years to treat patients with osteoporosis, with the benefits of increased bone density. Its osteo-anabolic action has led to the investigation of the use of teriparatide for the improvement of bone quality. Apart from the enhancement of fracture union, teriparatide has been extensively studied in the promotion of fusion rate after spinal fusion. This study summarizes the preclinical and clinical results of the off-label use of teriparatide in the spine, and specifically its intermittent administration after instrumented spinal arthrodesis along with its impact on the spinal bone quality and spinal bone mineral density.