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Multiple myeloma (MM) is a blood cancer caused by uncontrolled growth of clonal plasmacells. Bone disease is responsible for the severe complications of MM and is caused by myeloma cells infiltrating the bone marrow and inducing osteoclast activation. To date, no treatment for MM is truly curative since patients relapse and become refractory to all drug classes. Cannabinoids are already used as palliative in cancer patients. Furthermore, their proper anticancer effect was demonstrated in many cancer models in vitro, in vivo, and in clinical trials. Anyway, few information was reported on the effect of cannabinoids on MM and no data has been provided on minor phytocannabinoids such as cannabigerol (CBG), cannabichromene (CBC), cannabinol (CBN), and cannabidivarin (CBDV). Scientific literature also reported cannabinoids beneficial effect against bone disease. Here, we examined the cytotoxic activity of CBG, CBC, CBN, and CBDV in vitro in MM cell lines, their effect in modulating MM cells invasion toward bone cells and the bone resorption. Subsequently, according to the in vitro results, we selected CBN for in vivo study in a MM xenograft mice model. Results showed that the phytocannabinoids inhibited MM cell growth and induced necrotic cell death. Moreover, the phytocannabinoids reduced the invasion of MM cells toward osteoblast cells and bone resorption in vitro. Lastly, CBN reduced in vivo tumor mass. Together, our results suggest that CBG, CBC, CBN, and CBDV can be promising anticancer agents for MM. [ABSTRACT FROM AUTHOR]

Background: Focal unspecific bone uptake (UBU) is common in [18F]PSMA-1007 PET/CT, yet its clinical significance remains unclear, causing uncertainty in treatment decisions. Material and Methods: We retrospectively analyzed 99 prostate cancer patients (age 69 ± 7) who underwent [18F]PSMA-1007 PET/CT scans (3 MBq/kg; uptake time 70 ± 14 min) for staging and follow-up (after 13.0 ± 7.2 months). Semiquantitative assessment using the miPSMA score, analogous to the PROMISE criteria, evaluated the prevalence of UBU and bone metastases. Results: In the initial PET/CT scan, 56 patients had 230 lesions classified as UBU. A total of 19 patients were found to have bone metastases and UBU, while 24 patients had no focal bone uptake. UBU distribution was as follows: ribs (50%), spine (30%), pelvis (15%), and other sites (5%). There were no significant differences in age, Gleason score, injected tracer dose, uptake time, SUVpeak of UBU, or SUVmean in the spleen and parotid gland between patients with and without UBU. Follow-up showed stable miPSMA-score and CT appearance in 44/56 patients with UBU (79%), minor changes in 5/56 patients (8%), and new bone metastases in 7/56 patients (12%). Patient-specific analysis indicated at least one bone metastasis initially classified as UBU in 3/56 patients (5%) and new bone metastases in 4/56 patients (7%). In total, 4 of the 24 patients (17%) without initial focal uptake developed osseous metastases at follow-up. Conclusions: No significant differences were found between patients with or without UBU. Only a small portion of UBU (2%) evolved into metastases, a lower rate than the development of new osseous metastases, which appears to be independent of UBU. [ABSTRACT FROM AUTHOR]

Background: An increased prevalence of benign lesions has been associated with the increased use of radiological tools in orthopedic practice. Purpose: To investigate the inter-observer reliability of the radiographic detection of lesions on the proximal humerus between different observers. Material and Methods: X-ray radiological examinations of 17,243 patients were performed by an orthopedic surgeon to assess the presence of proximal humeral bone lesions. After this initial screening, 201 patients with lesions were identified and these 201 scans were assessed by three different physicians: an orthopedic oncologist, an orthopedic surgeon, and a musculoskeletal radiologist. Of the 201 patients with lesions, 80 had magnetic resonance imaging in addition to X-rays and were assessed. The diagnosis of the lesions was determined by each participant according to their radiological appearance to assess inter-observer reliability. Results: The prevalence of proximal humeral lesions was determined by the orthopedic surgeon to be 1.165% (201 of 17,243 patients). In 201 patients with a lesion, the mean age was 48 ± 17 years (range = 18–91 years). According to the assessments of the orthopedic oncologist, orthopedic surgeon, and musculoskeletal radiologist, the most common bone lesion identified was enostosis, with prevalence percentages of 53.7%, 59.7%, and 64.7%, respectively. A noteworthy consensus exists in the collective diagnosis of bone lesions among the three investigators, demonstrated by a substantial agreement with Fleiss' κ at 0.74 (P < 0.001). Conclusion: There was remarkable agreement between the three investigators on the collective diagnosis of bone lesions. Enostosis was the most common bone lesion at the proximal humerus in our series. [ABSTRACT FROM AUTHOR]

Objective: To determine if macroscopic intralesional fat detected in bone lesions on CT by Hounsfield unit (HU) measurement and on MRI by macroscopic assessment excludes malignancy. Materials and methods: All consecutive CT-guided core needle biopsies (CNB) of non-spinal bone lesions performed at a tertiary center between December 2005 and September 2021 were reviewed. Demographic and histopathology data were recorded. All cases with malignant histopathology were selected, and imaging studies were reviewed. Two independent readers performed CT HU measurements on all bone lesions using a circular region of interest (ROI) to quantitate intralesional fat density (mean HU < −30). MRI images were reviewed to qualitatively assess for macroscopic intralesional fat signal in a subset of patients. Inter-reader agreement was assessed with Cronbach's alpha and intraclass correlation coefficient. Results: In 613 patients (mean age 62.9 years (range 19–95 years), 47.6% female), CT scans from the CNB of 613 malignant bone lesions were reviewed, and 212 cases had additional MRI images. Only 3 cases (0.5%) demonstrated macroscopic intralesional fat on either CT or MRI. One case demonstrated macroscopic intralesional fat density on CT in a case of metastatic prostate cancer. Two cases demonstrated macroscopic intralesional fat signal on MRI in cases of chondrosarcoma and osteosarcoma. Inter-reader agreement was excellent (Cronbach's alpha, 0.95–0.98; intraclass correlation coefficient, 0.90–0.97). Conclusion: Malignant lesions rarely contain macroscopic intralesional fat on CT or MRI. While CT is effective in detecting macroscopic intralesional fat in primarily lytic lesions, MRI may be better for the assessment of heterogenous and infiltrative lesions with mixed lytic and sclerotic components. Clinical relevance statement: Macroscopic intralesional fat is rarely seen in malignant bone tumors and its presence can help to guide the diagnostic workup of bone lesions. Key Points: • Presence of macroscopic intralesional fat in bone lesions has been widely theorized as a sign of benignity, but there is limited supporting evidence in the literature. • CT and MRI are effective in evaluating for macroscopic intralesional fat in malignant bone lesions with excellent inter-reader agreement. • Macroscopic intralesional fat is rarely seen in malignant bone lesions. [ABSTRACT FROM AUTHOR]

Abstract Background Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion. Methods The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma. Results We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient’s imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma. Conclusions Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion.

Animal domestication led to changes in the interaction between animals and humans, including new ways of exploitation, which could potentially leave lesions on the animals' bones. This study aims to examine changes in the prevalence of pathological manifestation following changes in human‐animal interactions as a result their domestication. For this purpose, we studied 19,565 animal remains recovered from archaeological excavations, dated from the Pre‐Pottery Neolithic period to historical periods and assigned the pathologies into types. Of these, 60 animal remains presented pathological lesions. The suspected pathological cases were validated using a microscope, X‐ray, and/or micro‐CT scan. Lesions were divided into four categories: trauma, aging/musculoskeletal stress marks (MSM), periodontal diseases, and inflammatory processes. Then, our database was combined with previously published data to a total of 26,596 animal remains, out of which 128 demonstrated pathological lesions. We found that the prevalence of lesions in animals was higher in the historical periods compared with prehistoric periods. Moreover, based on a comparison between recent gazelles living in captivity and those living in the wild, we found that captivity resulted in the deterioration of the animals' health. We concluded that pathologies were more frequent in livestock in historic periods, in comparison with wild species and livestock from earlier periods. Such lesions were common not only in working livestock (cattle and donkeys) but also in non‐working domesticates (caprines and chickens) and companion animals (dogs and cats). Variations in the pathological frequencies between these three categories may be attributed to differences in exploitation, including the intensification of farming and herding. Finally, this study provides a unique reference dataset for zooarchaeologists when studying ancient animal assemblages. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is an imaging technique that has demonstrated high sensitivity and specificity in detecting prostate cancer and its metastasis, especially in the bones. This case describes a 60-year-old man who presented for increased prostate-specific antigen (PSA) level and underwent [68Ga]gallium-PSMA-11 PET/CT imaging for better disease assessment. 68Ga-PSMA-11 PET/CT revealed numerous radiotracer-positive lesions in both prostate lobes with associated sclerotic lesions on L4 and L5, but only L5 showed increased radiotracer avidity raising the possibility of metastasis. Magnetic Resonance Imaging (MRI) raises the possibility of aggressive MODIC type 1 lesion vs. infectious/inflammatory process. A biopsy of the radiotracer avid area was performed and showed no evidence of metastasis. The final diagnosis was aggressive MODIC type 1, in keeping with the false positive result of 68Ga-PSMA-11 PET/CT. This example demonstrates the possible limitations of 68Ga-PSMA-11 PET/CT, particularly in detecting bone metastases, and emphasizes the need for cautious interpretation and additional study to improve its diagnostic accuracy. Understanding and resolving these limitations is critical for increasing the accuracy of PSMA PET/CT in prostate cancer management. [ABSTRACT FROM AUTHOR]

Background: Leukocyte Ig-like receptor B family 4 (LILRB4) as an immune checkpoint on myeloid cells is a potential target for tumor therapy. Extensive osteolytic bone lesion is the most characteristic feature of multiple myeloma. It is unclear whether ectopic LILRB4 on multiple myeloma regulates bone lesion. Methods: The conditioned medium (CM) from LILRB4-WT and -KO cells was used to analyze the effects of LILRB4 on osteoclasts and osteoblasts. Xenograft, syngeneic and patient derived xenograft models were constructed, and micro-CT, H&E staining were used to observe the bone lesion. RNA-seq, cytokine array, qPCR, the activity of luciferase, Co-IP and western blotting were used to clarify the mechanism by which LILRB4 mediated bone damage in multiple myeloma. Results: We comprehensively analyzed the expression of LILRB4 in various tumor tissue arrays, and found that LILRB4 was highly expressed in multiple myeloma samples. The patient's imaging data showed that the higher the expression level of LILRB4, the more serious the bone lesion in patients with multiple myeloma. The conditioned medium from LILRB4-WT not -KO cells could significantly promote the differentiation and maturation of osteoclasts. Xenograft, syngeneic and patient derived xenograft models furtherly confirmed that LILRB4 could mediate bone lesion of multiple myeloma. Next, cytokine array was performed to identify the differentially expressed cytokines, and RELT was identified and regulated by LILRB4. The overexpression or exogenous RELT could regenerate the bone damage in LILRB4-KO cells in vitro and in vivo. The deletion of LILRB4, anti-LILRB4 alone or in combination with bortezomib could significantly delay the progression of bone lesion of multiple myeloma. Conclusions: Our findings indicated that LILRB4 promoted the bone lesion by promoting the differentiation and mature of osteoclasts through secreting RELT, and blocking LILRB4 singling pathway could inhibit the bone lesion. [ABSTRACT FROM AUTHOR]

Purpose: Fibrous dysplasia (FD) is a rare genetic disease with benign bone tumors. FD can affect one (monostotic FD) or multiple bones (polyostotic FD), with craniofacial lesions being common. Because of its rarity, there are only few clinical reports on FD in the head and neck region and its clinical characteristics remain incompletely defined. This study aimed to determine patient demographics, symptoms, diagnostics, and given treatment in patients with FD of the head and neck in a Finnish population. Methods: A retrospective review on all patients diagnosed with or treated for FD of the head and neck at the Helsinki University Hospital during 2005–2020. Results: In total 74 patients were identified; 54% were male and the mean age 45 years. Overall 95% had monostotic FD. Mandibula and maxilla were the most common anatomic sites. Majority of patients had symptoms, most commonly pain and lesion growth, and 49% had extra-skeletal symptoms. For all, diagnosis was primarily based on imaging findings, biopsies were obtained from 41%. Altogether 54 patients (73%) were managed by observation only, 20 patients (27%) received treatment; ten bisphosphonates, six surgery and four both. Conclusion: Although highly variable in its clinical manifestations, head and neck FD lesions are often symptomatic and impose risk for extra-skeletal complications. Treatment is often conservative but should be individually tailored. Future studies are encouraged to better define the disease characteristics and hopefully offer new treatment possibilities. [ABSTRACT FROM AUTHOR]

Fibrous dysplasia (FD) is a rare bone disorder characterized by the replacement of normal bone with benign fibro-osseous tissue. Developments in our understanding of the pathophysiology and treatment options are impeded by the lack of suitable research models. In this study, we developed an in vitro organotypic model capable of recapitulating key intrinsic and phenotypic properties of FD. Initially, transcriptomic profiling of individual cells isolated from patient lesional tissues unveiled intralesional molecular and cellular heterogeneity. Leveraging these insights, we established patient-derived organoids (PDOs) using primary cells obtained from patient FD lesions. Evaluation of PDOs demonstrated preservation of fibrosis-associated constituent cell types and transcriptional signatures observed in FD lesions. Additionally, PDOs retained distinct constellations of genomic and metabolic alterations characteristic of FD. Histological evaluation further corroborated the fidelity of PDOs in recapitulating important phenotypic features of FD that underscore their pathophysiological relevance. Our findings represent meaningful progress in the field, as they open up the possibility for in vitro modeling of rare bone lesions in a three-dimensional context and may signify the first step towards creating a personalized platform for research and therapeutic studies. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is a rare disease with limited treatment options. We present a case involving a 57-year-old woman afflicted with an isolated LCH bone osteolytic lesion. A single bisphosphonate infusion significantly alleviated pain, and follow-up scans via CT, PET-CT, and MRI revealed a substantial recalcification of the lesion. Conducting an extensive literature review, we identified 46 cases documenting the efficacy of bisphosphonates in the context of LCH. These findings have raised interest in bisphosphonate infusion as a simple therapeutic alternative in similar situations, with benefits in terms of bone recalcification and pain control for individuals with LCH. [ABSTRACT FROM AUTHOR]

Prostate-specific membrane antigen (PSMA) positron emission tomography/computed tomography (PET/CT) is an imaging technique that has demonstrated high sensitivity and specificity in detecting prostate cancer and its metastasis, especially in the bones. This case describes a 60-year-old man who presented for increased prostate-specific antigen (PSA) level and underwent [68Ga]gallium-PSMA-11 PET/CT imaging for better disease assessment. 68Ga-PSMA-11 PET/CT revealed numerous radiotracer-positive lesions in both prostate lobes with associated sclerotic lesions on L4 and L5, but only L5 showed increased radiotracer avidity raising the possibility of metastasis. Magnetic Resonance Imaging (MRI) raises the possibility of aggressive MODIC type 1 lesion vs. infectious/inflammatory process. A biopsy of the radiotracer avid area was performed and showed no evidence of metastasis. The final diagnosis was aggressive MODIC type 1, in keeping with the false positive result of 68Ga-PSMA-11 PET/CT. This example demonstrates the possible limitations of 68Ga-PSMA-11 PET/CT, particularly in detecting bone metastases, and emphasizes the need for cautious interpretation and additional study to improve its diagnostic accuracy. Understanding and resolving these limitations is critical for increasing the accuracy of PSMA PET/CT in prostate cancer management.

This is a rare case report of a young adult with oral manifestations of Langerhans cell histiocytosis (LCH). The initial symptom was localized severe bone loss in the mandible. Subsequently, thorough investigations led to a definitive diagnosis of multisystem LCH, a very rare histiocytic neoplasia. The relevance of more recent imaging modalities in the timely diagnosis and treatment of these uncommon lesions is also highlighted in our case study.

Background: Focal unspecific bone uptake (UBU) is common in [18F]PSMA-1007 PET/CT, yet its clinical significance remains unclear, causing uncertainty in treatment decisions. Material and Methods: We retrospectively analyzed 99 prostate cancer patients (age 69 ± 7) who underwent [18F]PSMA-1007 PET/CT scans (3 MBq/kg; uptake time 70 ± 14 min) for staging and follow-up (after 13.0 ± 7.2 months). Semiquantitative assessment using the miPSMA score, analogous to the PROMISE criteria, evaluated the prevalence of UBU and bone metastases. Results: In the initial PET/CT scan, 56 patients had 230 lesions classified as UBU. A total of 19 patients were found to have bone metastases and UBU, while 24 patients had no focal bone uptake. UBU distribution was as follows: ribs (50%), spine (30%), pelvis (15%), and other sites (5%). There were no significant differences in age, Gleason score, injected tracer dose, uptake time, SUVpeak of UBU, or SUVmean in the spleen and parotid gland between patients with and without UBU. Follow-up showed stable miPSMA-score and CT appearance in 44/56 patients with UBU (79%), minor changes in 5/56 patients (8%), and new bone metastases in 7/56 patients (12%). Patient-specific analysis indicated at least one bone metastasis initially classified as UBU in 3/56 patients (5%) and new bone metastases in 4/56 patients (7%). In total, 4 of the 24 patients (17%) without initial focal uptake developed osseous metastases at follow-up. Conclusions: No significant differences were found between patients with or without UBU. Only a small portion of UBU (2%) evolved into metastases, a lower rate than the development of new osseous metastases, which appears to be independent of UBU.

Objectives: Aim of this study was to retrospectively evaluate an interdisciplinary consultation followed by a precision‐based exercise program (PEP) for myeloma patients with stable and unstable bone lesions. Methods: Data of myeloma patients (n = 100) who received a PEP according to an orthopedic evaluation were analyzed. Bone stability was assessed by established scoring systems (Spinal Instability Neoplastic Score [SINS], Mirels' score). All patients with stable and unstable osteolyses received a PEP and n = 91 were contacted for a follow‐up interview. Results: In 60% of patients at least one osteolysis of the spine was considered potentially unstable or unstable. Following consultation, the number of patients performing resistance training could be significantly increased (≥2 sessions/week, 55%). Musculoskeletal pain was reported frequently. At the follow‐up interview, 75% of patients who performed PEP stated that painful symptoms could be effectively alleviated by exercise. Moreover, only patients who exercised regularly discontinued pain medication. No injuries were reported in association with PEP. Conclusion: We were able to demonstrate that individualized resistance training is implementable and safe for myeloma patients. By means of a PEP, patients' self‐efficacy in managing musculoskeletal pain was enhanced and pain medication could be reduced. [ABSTRACT FROM AUTHOR]

Bone metastases cause morbidity and mortality in several human cancer forms. Experimental models are used to unravel the mechanisms and identify possible treatment targets. The location inside the skeleton complicates accurate assessment. This study evaluates the performance of magnetic resonance imaging (MRI) of prostate cancer tumors growing intratibially in mice. MRI detected intratibial tumor lesions with a sensitivity and specificity of 100% and 89%, respectively, compared to histological evaluation. Location and some phenotypical features could also be readily detected with MRI. Regarding volume estimation, the correlation between MRI and histological assessment was high (p < 0.001, r = 0.936). In conclusion, this study finds MRI to be a reliable tool for in vivo, non-invasive, non-ionizing, real-time monitoring of intratibial tumor growth. [ABSTRACT FROM AUTHOR]

Multicentric osteosarcoma (M-OGS) is classified as a special type of osteosarcoma, which is characterized by multicentric bone lesions without visceral organs involvement in the tumor process. Synchronous type of the lesion is noted when several foci of osteosarcoma are diagnosed at the same time, whereas metachronous type may develop additional foci 6 months after the primary tumor diagnosis. This type of osteosarcoma is very rare with only a few articles describing this pathology. Objective. Present a clinical case of rare pathology -- multicentric osteosarcoma. Materials and methods. Clinical, radiological, pathomorphological data of a patient with multicentric osteosarcoma. Data on the results of treatment of the patient. Results. Multicentric osteosarcoma It accounts for about 1.5 % of all cases reported worldwide. Fuchs et al described a multifactorial etiology of this pathology, considering it a part of hereditary diseases, such as Rothmund-Thomson, Bloom syndromes. Patients with Pagetʼs disease or McCune-Albright syndrome have also been diagnosed with multicentric M-OGS. Tumor genetic predisposition has been described as one of the etiology factors, where a genetic mutation is detected. While studying the nature of multicentric M-OGS, various scientists have created classifications of this lesion. Taking to account all clinical and radiological data, a differential diagnosis comes to multiple metastatic lesions of carcinoma, chronic recurrent osteomyelitis and hyperphosphatasia. Conclusions. Multicentric osteosarcoma is a highly malignant and aggressive tumor that has a characteristic clinical presentation in the form of multiple bone lesions without visceral organs involvement. Mandatory patient monitoring after a comprehensive treatment allows to detect a spread of tumor process, as well as verify this rare pathology and choose the best treatment course. [ABSTRACT FROM AUTHOR]

Fibrous dysplasia (FD) is a rare bone disorder characterized by the replacement of normal bone with benign fibro-osseous tissue. Developments in our understanding of the pathophysiology and treatment options are impeded by the lack of suitable research models. In this study, we developed an in vitro organotypic model capable of recapitulating key intrinsic and phenotypic properties of FD. Initially, transcriptomic profiling of individual cells isolated from patient lesional tissues unveiled intralesional molecular and cellular heterogeneity. Leveraging these insights, we established patient-derived organoids (PDOs) using primary cells obtained from patient FD lesions. Evaluation of PDOs demonstrated preservation of fibrosis-associated constituent cell types and transcriptional signatures observed in FD lesions. Additionally, PDOs retained distinct constellations of genomic and metabolic alterations characteristic of FD. Histological evaluation further corroborated the fidelity of PDOs in recapitulating important phenotypic features of FD that underscore their pathophysiological relevance. Our findings represent meaningful progress in the field, as they open up the possibility for in vitro modeling of rare bone lesions in a three-dimensional context and may signify the first step towards creating a personalized platform for research and therapeutic studies.

Salmonella osteomyelitis is an underdiagnosed pathology with unusual clinical presentations. The patient was a 24-year-old female with no previous medical history who presented to the emergency department with progressive pain in the left arm for several months. She was initially treated unsuccessful with augmentin for 7 days for suspicious cellulites. Standard elbow X-rays described a lesion initially considered as metastatic. Investigations were completed with magnetic resonance imaging (MRI) compatible with osteomyelitis. Following surgical sampling, salmonella enterica infection was diagnosed. The patient recovered full use of her limb after 8 days of IV antibiotic therapy with third-generation cephalosporin, and she completed 11 weeks of antibiogram-targeted PO fluoroquinolone therapy. Salmonella osteomyelitis could mimic other diseases, making diagnosis difficult.

Neurofibromatosis is an autosomal dominant neurocutaneous syndrome characterized by skin lesions and central or peripheral nervous system tumors. Although neurofibromatosis is a neurocutaneous disease, it also involves multiple systems. For example, bone lesions have been reported in 40% of patients. As in this case, pathologies associated with the mandible and temporomandibular joint in neurofibromatosis are rarely reported in the literature. In our case, we aimed to emphasize that skeletal malformations may also be present in the rich clinical picture of neurofibromatosis. Maxillofacial computed tomography of a 24-year-old female patient who was followed up at Selçuk University Hospital with a diagnosis of neurofibromatosis revealed an appearance compatible with atrophy in the right half of the mandible. The mandibular ramus was 41.27 mm on the right and 53.44 mm on the left; the diameter of the condyloid process was 10.31 mm on the right and 15.71 mm on the left. The joint distance was increased on the right. Radiologic examinations in neurofibromatosis syndrome should be performed considering the possibility of bone lesions. These examinations are especially important for the prevention of pathologic fractures in bones. [ABSTRACT FROM AUTHOR]

The aim of the given study is investigation of influence onosteodestruction markers and quality of life parameters of therapy with generic preparation of pamidronic acid (pomegara) in patients with multiple myeloma (MM) and lytic bone lesions. For this purpose prior to the beginning of the study and every 4 week after pomegara injection throughout 16 weeks blood СТХ (terminal crosslinking telopeptide of type I collagene) concentration and urine DPD (deoxypyridinoline) were detected. In addition monitoring of tumor symptoms intensity using MDASI (M.D. Anderson Symptom Inventory) and FACT (Functional Assessment of Cancer Therapy) questionnaires was conducted and pain intensity was also investigated using analogue scale. Study is finished in eighteen patients. Bone resorbtion markers (serum СТХ and urine DPD) have essential decreased after fourth pomegara injection to 33 % of median initial value for CTX (р < 0.05) and to 73 % – for DPD (р=ns). Statistically significant increasing of integrated quality of life parameter in comparison with initial value is registered by 12th week of treatment (р < 0.05). The majority of pomegara side effects were mild and moderate severity and preparation cancelling has not necessary. The frequency and spectrum of complications (fever, skeletal and muscular pain, etc.) corresponded to the similar parameters revealed in large controlled studies of bisphosphonate treatment in MM. Careful monitoring of renal function during pomegara treatment has not shown significant negative effect, including patients with initial renal involvement. According to data received in this restricted volume study we can conclude that pomegara treatment in patients with MM and lytic bone lesions result in decrease of bone destruction, quality of life improvement and decrease severity of pain. Drug acceptability did not principally differ from original pamidronate shown in controlled studies.

Brown tumors are benign bone tumors that rarely complicate hyperparathyroidism, manifesting as fibrous and erosive lesions secondary to rapid and localized osteoclast turnover. These lesions are typical of primary hyperparathyroidism, but they are not often observed. We present the case of a 72-year-old woman presenting with asthenia, bone pain, and hemiplegia. Biological analysis showed primary hyperparathyroidism, cervical ultrasound a right parathyroid adenoma that fixed on scintigraphy. When cross-sectional imaging was performed, it revealed multiple bone tumors of the axial and peripheral trunk with spinal cord compression which were diagnosed as brown tumors related to parathyroid adenoma. We illustrate through this case the importance of multidisciplinary imaging techniques before raising the diagnosis, especially in unusual pathologies such as brown tumors.

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Bone metastases cause morbidity and mortality in several human cancer forms. Experimental models are used to unravel the mechanisms and identify possible treatment targets. The location inside the skeleton complicates accurate assessment. This study evaluates the performance of magnetic resonance imaging (MRI) of prostate cancer tumors growing intratibially in mice. MRI detected intratibial tumor lesions with a sensitivity and specificity of 100% and 89%, respectively, compared to histological evaluation. Location and some phenotypical features could also be readily detected with MRI. Regarding volume estimation, the correlation between MRI and histological assessment was high (p < 0.001, r = 0.936). In conclusion, this study finds MRI to be a reliable tool for in vivo, non-invasive, non-ionizing, real-time monitoring of intratibial tumor growth.

Abstract Multiple myeloma is characterized by osteolytic lesions caused by reduced bone formation and activated bone resorption. An important feature of myeloma is a failure of bone healing after successful treatment. In this work, clinical studies indicated a highly positive correlation between bone marrow bacteria abundance and bone lesion numbers of myeloma patients in complete remission. Coculture experiments demonstrated that marrow Escherichia coli (E. coli) promotes osteoclast differentiation and inhibits osteoblast differentiation. Mechanism studies showed that E. coli lipopolysaccharides (LPS) activated NF-κB p65 signaling and reduced phosphorylated smad1/5/9 binding ability with RUNX2 promoter, leading to decreased RUNX2 expression in osteoblast progenitors. Additionally, LPS enhanced phosphorylated NF-κB p65 binding ability with NFATc1 promoter, leading to increased NFATc1 expression in osteoclast progenitors. In vivo studies revealed E. coli contributes to osteolytic bone lesion, and elimination of E. coli infection assists healing of bone lesion in mouse model of myeloma in complete remission. These findings establish a heretofore unrecognized effect for E. coli in the genesis of myeloma bone disease and suggest a new treatment strategy.

Background: ECD is a rare non-Langerhans cell histiocytosis with diverse and heterogeneous clinical manifestations, ranging from single-lesion forms to multi-system involvement, including slowly progressing unifocal forms to rapidly evolving life-threatening disease. Case presentation: A female patient presented with a 2-month history of fever. Imaging revealed multiple thromboses, bone destruction, an abnormal pituitary stalk, and clinical manifestations of diabetes insipidus. Excisional biopsy of a tibial lesion was sent for microscopic examination, and subsequent immunohistochemical testing was positive for expression of CD68 and CD163, and negative for expression of the immune markers CD1a, S100, and langerin. This confirmed the diagnosis of ECD. Treatment with methylprednisolone to inhibit the immune inflammatory response along with anti-cytokine therapy with an interleukin-6 antagonist resulted in satisfactory disease control. Conclusion: We report a rare case of multiple thromboses, embolism, and multiple organ involvement as the main presentation of ECD, suggesting that ECD should be considered in patients presenting with multiple thromboses associated with multisystem damage. We successfully treated our patient with glucocorticoids and interleukin-6 antagonist. This patient's response to treatment suggests that hormone therapy and cytokine/chemokine therapy may be a potential novel treatment for patients with ECD without gene mutations. [ABSTRACT FROM AUTHOR]

Bartonella henselae is an unusual and rarely suspected osteomyelitis etiologic agent. We present a case of low back‐pain in a 10‐year‐old female which lead to a challenging diagnostic work‐up due to subtle imaging findings. The diagnosis was Bartonella henselae vertebral osteomyelitis mimicking bone tumor. Bartonella infection should be included in the differential diagnosis of pediatric back pain associated with fever, especially if there is a history of exposure to cats. MRI is the most sensitive radiographic technique to define bone lesions, but in case of non‐specific findings, the biopsy of the lesion is mandatory. [ABSTRACT FROM AUTHOR]

Abstract Objective: To investigate the involvement of IL-6/STAT3 signaling pathway activation in macrophage polarization and bone destruction related to apical periodontitis (AP) stimulated by Porphyromonas gingivalis. Methodology: Macrophage polarization, IL-6/STAT3 expression, and the presence of P. gingivalis were detected in human AP tissues via RT-qPCR, western blotting, and immunohistochemistry staining. Murine bone marrow derived macrophages were isolated and cultured with P. gingivalis W83 in vitro, and levels of macrophage IL-6 expression, STAT3 phosphorylation, and macrophage polarization with or without the selective STAT3 phosphorylation inhibitor Stattic (5 μM) were detected via ELISA, western blotting, RT-qPCR, and flow cytometry, respectively. P. gingivalis-induced murine AP models were constructed, and bone destruction and macrophage polarization in the apical region were evaluated. Transwell co-culture systems were used to investigate the effects of macrophages infected with P. gingivalis on osteogenesis and osteoclastogenesis. Results: P. gingivalis was detected in human AP tissues that highly expressed IL-6/STAT3, and the M1 subtype of macrophages was more abundant in these tissues. P. gingivalis infection induced IL-6 expression, STAT3 phosphorylation, and M1 polarization of macrophages, while 5 μM of Stattic partially abolished these activation effects. Systemic STAT3 blockade via oral administration of Stattic at a dose of 25 mg kg-1 alleviated murine periapical bone resorption and apical infiltration of M1 macrophages induced by P. gingivalis infection in vivo. Furthermore, macrophages infected with P. gingivalis promoted bone destruction via secretion of IL-6, TNF-α, and RANKL, which hinder pre-osteoblast expression of Runx2 and accelerate pre-osteoclast expression of NFAT2. Conclusions: The activation of IL-6/STAT3 signaling pathway is involved in mediating macrophages M1 polarization in the P. gingivalis induced apical inflammatory context and may also be intimately involved in the bone loss caused by P. gingivalis infection, directing the M1 macrophage infiltration during the progression of AP.

Abstract Bartonella henselae is an unusual and rarely suspected osteomyelitis etiologic agent. We present a case of low back‐pain in a 10‐year‐old female which lead to a challenging diagnostic work‐up due to subtle imaging findings. The diagnosis was Bartonella henselae vertebral osteomyelitis mimicking bone tumor.

Teaching Point: Cemento-ossifying fibromas are rare, benign tumours that are mostly found in the tooth-bearing areas of the mandible or maxilla and can be seen on cone-beam computed tomography.

Aneurysmal bone cyst is a benign highly vascular lesion that occurs in children. Traditionally ABCs were treated by surgical resection. However, lesions at difficult to access anatomical locations such as the pelvis have higher morbidity when treated surgically. Recently with the advances in endovascular treatment selective arterial embolization became a promising option for primary treatment of ABC. The authors present a case of a 14-year-old female with a pelvic ABC that was successfully treated by selective arterial embolization. Selective arterial embolization is a cost-efficient way of managing ABC especially in cases where surgical treatment carries high risk.

Abstract Background This study aimed to identify the characteristic radiological signs for the diagnosis of Langerhans cell histiocytosis (LCH) of the bone. Methods We retrospectively studied 82 cases of LCH with bone lesions confirmed by pathology. Clinical and radiological features of the patients were analyzed. Results A total of 64 and 18 patients had single and multiple bone lesions, respectively. With regard to LCH with single bone lesions, 37.5% (24/64) of lesions were located in the skull and presented as bone destruction with or without soft tissue mass. The correct diagnosis rate of these lesions was 60.0% (9/15) in children and adolescents, but was only 22.2% (2/9) in adults. A total of 26.5% (17/64) of the solitary lesions were found in the spine. Of these, 88.2% (15/17) were located in the vertebral body and appeared to have different degrees of collapse, and 66.7% (10/15) of these lesions were correctly diagnosed. Of the unifocal lesions, 21.8% (14/64) were located in other flat and irregular bones and manifested as osteolysis. Only 21.4% (3/14) of these cases were correctly diagnosed. In total, 14.1% (9/64) of the isolated bone LCH lesions were located in the long bones. Of these, 77.8% (7/9) were located in the diaphysis and presented as central bone destruction with or without fusiform periosteal reaction and extensive peripheral edema, of which 42.9% (3/7) were correctly diagnosed before surgery or biopsy. With regard to LCH with multiple bony destructive lesions, 71.4% (10/14) of cases in children and adolescents were correctly diagnosed; however, all four cases among adults were misdiagnosed. Conclusion In all age groups, isolated diaphyseal destruction of the long bone with fusiform periosteal reaction and extensive peripheral edema, vertebra plana of the spine, and bevelled edge of skull defects accompanied by soft tissue masses strongly suggest LCH diagnosis. Moreover, the multiple bone osteolytic destruction in children and adolescents strongly suggests LCH diagnosis. Familiarity with these typical radiological signs of LCH is necessary to decrease misdiagnoses.

Abstract Background Langerhans cell histiocytosis (LCH) is a rare disease that originates from the uncontrolled proliferation and accumulation of bone marrow-derived immature myeloid dendritic cells. Dendritic cells are a type of histiocyte that play an important role in the human immune system and are found in the bone, skin, stomach, eyes, intestines, and lungs. Objective This systematic review aimed to collect and report published case reports of rare bone disease caused by LCH to avoid misdiagnoses or delays in diagnosis. Methods We systematically searched Scopus, PubMed, Embase, and Web of Sciences from August 1, 2000 to December 31, 2019. Studies reporting cases of LCH with rare bone involvement were included. Results We identified 60 articles including 64 cases. Of the identified cases, 31 (48.4%) involved children, and 33 (51.6%) involved adults. Additionally, 46.9% (30 individuals) were from Asian countries. The mean age of the children was 7.6 ± 4.3 years and that of the adults was 36 ± 12 years. The findings indicated that unifocal bone involvements were the most prevalent form of the disease (68.7%), and, overall, the skull and chest wall were the most commonly affected bones in both adults and children. The spine and long bones were the second most commonly affected bones in children, and the spine and jaw were the second most commonly affected bones in adults. Pain and swelling were the most frequent presenting signs among the investigated cases, and loss of consciousness, myelopathy, nerve palsy, visual loss, torticollis and clicking sounds were rare signs. Osteolytic lesions were the most frequent radiologic feature (62.5%), and intracranial hemorrhage, fluid–fluid level, dura and intracranial extension and pathologic fractures were rare radiological features. Total excision, curettage and observation in the unifocal group of patients and systemic chemotherapy in the other groups (i.e., multifocal and multisystem) were the most frequent management approaches. The recovery rates of the unifocal and multifocal groups were 77.3% and 81.8%, respectively, while that of the multisystem group was 55.5%. The rates of recurrence and mortality in the multisystem group were 11% and were higher than those in the other groups. Conclusions LCH is a rare disease that can affect any organ in the human body. However, bone is the most commonly involved organ, and rare bone involvements may be the first or only symptom of the disease due to the rarity of such lesions; a lack of familiarity with them may result in misdiagnosis or delayed diagnosis.

In this study, we formulated an efficient deep learning-based classification strategy for characterizing metastatic bone lesions using computed tomography scans (CTs) of prostate cancer patients. For this purpose, 2,880 annotated bone lesions from CT scans of 114 patients diagnosed with prostate cancer were used for training, validation, and final evaluation. These annotations were in the form of lesion full segmentation, lesion type and labels of either benign or malignant. In this work, we present our approach in developing the state-of-the-art model to classify bone lesions as benign or malignant, where (1) we introduce a valuable dataset to address a clinically important problem, (2) we increase the reliability of our model by patient-level stratification of our dataset following lesion-aware distribution at each of the training, validation, and test splits, (3) we explore the impact of lesion texture, morphology, size, location, and volumetric information on the classification performance, (4) we investigate the functionality of lesion classification using different algorithms including lesion-based average 2D ResNet-50, lesion-based average 2D ResNeXt-50, 3D ResNet-18, 3D ResNet-50, as well as the ensemble of 2D ResNet-50 and 3D ResNet-18. For this purpose, we employed a train/validation/test split equal to 75%/12%/13% with several data augmentation methods applied to the training dataset to avoid overfitting and to increase reliability. We achieved an accuracy of 92.2% for correct classification of benign vs. malignant bone lesions in the test set using an ensemble of lesion-based average 2D ResNet-50 and 3D ResNet-18 with texture, volumetric information, and morphology having the greatest discriminative power respectively. To the best of our knowledge, this is the highest ever achieved lesion-level accuracy having a very comprehensive data set for such a clinically important problem. This level of classification performance in the early stages of metastasis development bodes well for clinical translation of this strategy.

Multiple myeloma is characterized by osteolytic lesions caused by reduced bone formation and activated bone resorption. An important feature of myeloma is a failure of bone healing after successful treatment. In this work, clinical studies indicated a highly positive correlation between bone marrow bacteria abundance and bone lesion numbers of myeloma patients in complete remission. Coculture experiments demonstrated that marrow Escherichia coli (E. coli) promotes osteoclast differentiation and inhibits osteoblast differentiation. Mechanism studies showed that E. coli lipopolysaccharides (LPS) activated NF-κB p65 signaling and reduced phosphorylated smad1/5/9 binding ability with RUNX2 promoter, leading to decreased RUNX2 expression in osteoblast progenitors. Additionally, LPS enhanced phosphorylated NF-κB p65 binding ability with NFATc1 promoter, leading to increased NFATc1 expression in osteoclast progenitors. In vivo studies revealed E. coli contributes to osteolytic bone lesion, and elimination of E. coli infection assists healing of bone lesion in mouse model of myeloma in complete remission. These findings establish a heretofore unrecognized effect for E. coli in the genesis of myeloma bone disease and suggest a new treatment strategy. [ABSTRACT FROM AUTHOR]

Background: Bone lesions of Langerhans cell histiocytosis (LCH) may be triggered by trauma. Methods: The characteristics of pediatric patients in the JLSG-02 study cohort who developed a bone lesion at the trauma site at diagnosis of LCH were analyzed retrospectively. Results: Of the 261 pediatric patients with LCH, 12 (4.6%), of median age 4.9 years, had trauma-triggered bone LCH lesions at diagnosis, making them significantly older than the remaining patients (P = 0.006). Trauma sites included the craniofacial regions in 10 patients and the lumbar spine and pelvis in one patient each. At the time of trauma, six patients had a bump at the site, whereas none had extradural hematomas or bone fractures. The median time from trauma to onset was 4 weeks. Of these 12 patients, three had isolated bone (IB) disease; four had multifocal bone (MFB) disease, including the bone lesion at the trauma site; and five had multisystem disease, including four with lesions in neighboring tissue and one with polyuria (posterior pituitary lesion) more than 1 year before the trauma-triggered bone lesion. Treatment responses were good in all 12 patients and none died, but relapses were observed in two patients, one each with IB and MFB disease. Conclusions: About 5% of pediatric patients with LCH developed new trauma-triggered bone lesions at a relatively old age. These lesions can manifest as IB, or, in patients with underlying LCH diseases, as MFB or multisystem. Good clinical outcomes were observed in these patients. [ABSTRACT FROM AUTHOR]

Langerhans cell histiocytosis (LCH) is a rare disease characterized by inflammatory neoplastic proliferation by of myeloid precursor cells with a high affinity for bone and skin but may affect any organ. The clinical manifestation of LCH varies between single lesions that may show spontaneous resolvement to life-threatening multisystem disease. Treatments used are surgical interference, local radiotherapy, chemotherapy or sometimes a combination of these approaches. Intralesional injections of steroids have been described to have a good outcome in single skeletal lesions of LCH. This report presents two male patients, 6 and 9-years old, with LCH affecting the right posterior mandible. Both were successfully treated with intralesional injection of methylprednisolone in one single session. Complete recovery was confirmed clinically and radiographically approximately 2 years after injection. [ABSTRACT FROM AUTHOR]

Osteolytic destruction is a hallmark of multiple myeloma and impairs myeloma patients’ quality of life. However, the molecular mechanism underlying the pathogenesis of myeloma-associated bone disease remains unclear. In this study, we demonstrate the role of myeloma cell-expressed integrin α6 in bone. Integrin α6 binds to laminin 8 and epidermal growth factor receptor on mesenchymal stem cells (MSCs) to form a trimer complex and upregulates the secretion of osteolytic cytokines from both myeloma cells and MSCs, leading to enhanced bone resorption and reduced bone formation. Thus, this study elucidates an important mechanism for myeloma-induced bone lesions and implicates that targeting integrin α6 may be a viable approach for bone healing in myeloma patients.

Background: Radiologists have difficulty distinguishing benign from malignant bone lesions because these lesions may have similar imaging appearances. The purpose of this study was to develop a deep learning algorithm that can differentiate benign and malignant bone lesions using routine magnetic resonance imaging (MRI) and patient demographics. Methods: 1,060 histologically confirmed bone lesions with T1- and T2-weighted pre-operative MRI were retrospectively identified and included, with lesions from 4 institutions used for model development and internal validation, and data from a fifth institution used for external validation. Image-based models were generated using the EfficientNet-B0 architecture and a logistic regression model was trained using patient age, sex, and lesion location. A voting ensemble was created as the final model. The performance of the model was compared to classification performance by radiology experts. Findings: The cohort had a mean age of 30±23 years and was 58.3% male, with 582 benign lesions and 478 malignant. Compared to a contrived expert committee result, the ensemble deep learning model achieved (ensemble vs. experts): similar accuracy (0·76 vs. 0·73, p=0·7), sensitivity (0·79 vs. 0·81, p=1·0) and specificity (0·75 vs. 0·66, p=0·48), with a ROC AUC of 0·82. On external testing, the model achieved ROC AUC of 0·79. Interpretation: Deep learning can be used to distinguish benign and malignant bone lesions on par with experts. These findings could aid in the development of computer-aided diagnostic tools to reduce unnecessary referrals to specialized centers from community clinics and limit unnecessary biopsies. Funding: This work was funded by a Radiological Society of North America Research Medical Student Grant (#RMS2013) and supported by the Amazon Web Services Diagnostic Development Initiative.

Osteolytic destruction is a hallmark of multiple myeloma and impairs myeloma patients' quality of life. However, the molecular mechanism underlying the pathogenesis of myeloma-associated bone disease remains unclear. In this study, we demonstrate the role of myeloma cell-expressed integrin α6 in bone. Integrin α6 binds to laminin 8 and epidermal growth factor receptor on mesenchymal stem cells (MSCs) to form a trimer complex and upregulates the secretion of osteolytic cytokines from both myeloma cells and MSCs, leading to enhanced bone resorption and reduced bone formation. Thus, this study elucidates an important mechanism for myeloma-induced bone lesions and implicates that targeting integrin α6 may be a viable approach for bone healing in myeloma patients. [ABSTRACT FROM AUTHOR]

Objective: The value of a bone biopsy in patients who present with a bone lesion and past medical history of malignancy is uncertain. The objective of this study was to evaluate the outcome of bone biopsies in patients with a history of a malignancy undergoing bone biopsy of a lesion in a regional bone tumour unit. Secondary outcomes include the assessment of survival in the different outcome groups. Materials and methods: This was a retrospective study of patients, with a previous malignancy and suspicious bone lesions, who underwent bone biopsy for final diagnosis between March 2010 and September 2019. Results of the biopsy were summarized into 3 groups: confirmed original malignancy, confirmed benign diagnosis, and confirmed new malignancy. Survival analysis of each group was also undertaken. Results: A total of 378 patients met the inclusion criteria (mean age 64 years, 216 females (57%)). In 250 cases (66%), the original malignancy was confirmed on the bone biopsy; in 128 cases, an alternative diagnosis was confirmed (benign diagnosis in 69 (18%)), and 59 had a new malignancy (16%). Survival was significantly greater for those in whom a benign diagnosis was confirmed (logrank test p = 0.0100). Conclusion: This study shows that for patients presenting with a suspicious bone lesion, together with a history of malignancy, in a third of cases, the bone biopsy will confirm an alternative diagnosis of a benign lesion or a new malignancy. Survival of these patients will vary significantly depending on the biopsy outcome. [ABSTRACT FROM AUTHOR]

Background: This study aimed to identify the characteristic radiological signs for the diagnosis of Langerhans cell histiocytosis (LCH) of the bone. Methods: We retrospectively studied 82 cases of LCH with bone lesions confirmed by pathology. Clinical and radiological features of the patients were analyzed. Results: A total of 64 and 18 patients had single and multiple bone lesions, respectively. With regard to LCH with single bone lesions, 37.5% (24/64) of lesions were located in the skull and presented as bone destruction with or without soft tissue mass. The correct diagnosis rate of these lesions was 60.0% (9/15) in children and adolescents, but was only 22.2% (2/9) in adults. A total of 26.5% (17/64) of the solitary lesions were found in the spine. Of these, 88.2% (15/17) were located in the vertebral body and appeared to have different degrees of collapse, and 66.7% (10/15) of these lesions were correctly diagnosed. Of the unifocal lesions, 21.8% (14/64) were located in other flat and irregular bones and manifested as osteolysis. Only 21.4% (3/14) of these cases were correctly diagnosed. In total, 14.1% (9/64) of the isolated bone LCH lesions were located in the long bones. Of these, 77.8% (7/9) were located in the diaphysis and presented as central bone destruction with or without fusiform periosteal reaction and extensive peripheral edema, of which 42.9% (3/7) were correctly diagnosed before surgery or biopsy. With regard to LCH with multiple bony destructive lesions, 71.4% (10/14) of cases in children and adolescents were correctly diagnosed; however, all four cases among adults were misdiagnosed. Conclusion: In all age groups, isolated diaphyseal destruction of the long bone with fusiform periosteal reaction and extensive peripheral edema, vertebra plana of the spine, and bevelled edge of skull defects accompanied by soft tissue masses strongly suggest LCH diagnosis. Moreover, the multiple bone osteolytic destruction in children and adolescents strongly suggests LCH diagnosis. Familiarity with these typical radiological signs of LCH is necessary to decrease misdiagnoses. [ABSTRACT FROM AUTHOR]

Several feasibility studies have reported that high-intensity focused ultrasound (HIFU) ablation can be applied to ease patients' bone pain. However, the effect of HIFU ablation to palliate bone pain remains unclear. To evaluate the technique's success, efficacy, minor complication and major complication on patients suffering from bone pain, we searched the PubMed, MEDLINE, EMBASE and Cochrane Library databases from January 1998 to March 2019. Clinical studies that have assessed the association between bone pain and HIFU ablation were involved. We filtered out 28 feasibility studies, which reported the association between HIFU ablation and bone pain, including a total of 717 patients and 736 bone lesions. Overall, our results indicate that the rate of technique success of HIFU ablation was 93% (95% confidence interval [CI] 89%-96%) for patients with bone lesions. The technique efficacy rate of HIFU ablation for palliation of pain from bone lesions was 80% (95% CI 74%-87%) in all the patients, 96% (91%-100%) in the subgroup of retrospective studies and 77% (69%-85%) in the subgroup of prospective studies. In regard to HIFU ablation treatment safety, the hazard ratio for minor complication was 12% (95% CI 7%-17%), and the hazard ratio for major complication was 2% (95% CI 1%-3%). In conclusion, the summary rates for various considerations of using HIFU ablation for the palliation of bone pain are as follows: technique success is 93%, technique efficacy is 77%, minor complication is 12% and major complication is 2%. Our results suggest that extracorporeal HIFU ablation is a promising method for palliation of pain in bone lesions, with high technique success and efficacy, but low adverse events. [ABSTRACT FROM AUTHOR]

Prostate cancer is the most common malignant tumor with bone metastasis, and there is still no ideal treatment for bone metastasis of prostate cancer. In this study, a pH and GSH dual sensitive calcium phosphate-polymer hybrid nanoparticle (DTX@Cap/HP) was prepared to co-deliver zoledronate (ZOL) and docetaxel (DTX) to treat bone metastasis of prostate cancer. DTX@Cap/HP exhibited high bone binding affinity and released more DTX and ZOL in acidic and high GSH concentration environment. A large amount of DTX@Cap/HP was uptaken by PC-3 cell in acidic medium than that in neutral medium. DTX@Cap/HP obviously reduced PC-3 cell proliferation and bone lesion in in-vitro 3D model of bone metastases of prostate cancer. Besides, DTX@Cap/HP also exhibited stronger anti bone metastases of prostate cancer activity in vivo as compared with the same dose of DTX + ZOL, which resulted from the co-delivery of DTX and ZOL to bone metastases of prostate cancer by DTX@Cap/HP and the synergistic effects of DTX and ZOL. DTX@Cap/HP has great potential in the treatment of bone metastases of prostate cancer. [ABSTRACT FROM AUTHOR]

Background: Langerhans cell histiocytosis (LCH) is a rare disease that originates from the uncontrolled proliferation and accumulation of bone marrow-derived immature myeloid dendritic cells. Dendritic cells are a type of histiocyte that play an important role in the human immune system and are found in the bone, skin, stomach, eyes, intestines, and lungs.Objective: This systematic review aimed to collect and report published case reports of rare bone disease caused by LCH to avoid misdiagnoses or delays in diagnosis.Methods: We systematically searched Scopus, PubMed, Embase, and Web of Sciences from August 1, 2000 to December 31, 2019. Studies reporting cases of LCH with rare bone involvement were included.Results: We identified 60 articles including 64 cases. Of the identified cases, 31 (48.4%) involved children, and 33 (51.6%) involved adults. Additionally, 46.9% (30 individuals) were from Asian countries. The mean age of the children was 7.6 ± 4.3 years and that of the adults was 36 ± 12 years. The findings indicated that unifocal bone involvements were the most prevalent form of the disease (68.7%), and, overall, the skull and chest wall were the most commonly affected bones in both adults and children. The spine and long bones were the second most commonly affected bones in children, and the spine and jaw were the second most commonly affected bones in adults. Pain and swelling were the most frequent presenting signs among the investigated cases, and loss of consciousness, myelopathy, nerve palsy, visual loss, torticollis and clicking sounds were rare signs. Osteolytic lesions were the most frequent radiologic feature (62.5%), and intracranial hemorrhage, fluid-fluid level, dura and intracranial extension and pathologic fractures were rare radiological features. Total excision, curettage and observation in the unifocal group of patients and systemic chemotherapy in the other groups (i.e., multifocal and multisystem) were the most frequent management approaches. The recovery rates of the unifocal and multifocal groups were 77.3% and 81.8%, respectively, while that of the multisystem group was 55.5%. The rates of recurrence and mortality in the multisystem group were 11% and were higher than those in the other groups.Conclusions: LCH is a rare disease that can affect any organ in the human body. However, bone is the most commonly involved organ, and rare bone involvements may be the first or only symptom of the disease due to the rarity of such lesions; a lack of familiarity with them may result in misdiagnosis or delayed diagnosis. [ABSTRACT FROM AUTHOR]

The subject matter of research in the article is the morphological structure of bone tissue in the lumbar spine, visualized by tomography in the sagittal and axial planes. The goal of the research is to create the most informative investigation method for analyzing the structure of bone tissue, taking into account pathology in the form of metastatic bone lesions. This is justified by the fact that the detection of pathological processes is one of the most important tasks of image processing and analysis; at the same time, early diagnosis of various pathologies, including cancer, significantly increases the chances of patient recovery. Tasks: to consider the existing modern methods for analyzing the structure of bone tissue, to develop and propose a method for detecting bone tissue pathology in multiple myeloma. For the development of methods for the analysis of tomographic images with lesion of the bone structure, one of the fundamental issues is visualization of tomographic data. In this case, it is advisable to provide modules for both two-dimensional and three-dimensional visualization with methods of processing and segmentation of vertebral bodies, as well as correcting the results obtained in an interactive mode. The research uses methods of improving the quality of images, filtering using adaptive local filters, segmentation and stereology methods, cluster analysis method. The result of the work is to obtain a method suitable for use in the analysis of bone tissue with its accompanying pathology in the form of bone metastases. This method will be the basis for the further development of a method aimed at analyzing the microstructure of bone tissue, which will significantly increase the accuracy of calculations. Conclusions. The relevance of the topic under study is of vital importance for a huge number of patients suffering from cancer. In the course of the research, algorithms for processing and analyzing input images were developed, taking into account the modality of the input data. This makes it possible to develop the next stage of analysis aimed at the microstructure of the bone tissue.

Background: Bone lesion in multiple myeloma (MM) is most commonly presented as a lytic lesion in this disease. Determination of extent of bone lesions in MM is necessary to follow-up the patients. Whole body bone scan with 99m, Tc-methylene diphosphonate (MDP) has a lower sensitivity than other modalities. Methods: From the patients with MM admitted to Ayatollah Rouhani Hospital of Babol-Iran from 2009 to 2015, who had undergone whole body bone scan during diagnostic process, were entered into the study. Findings of bone scan were compared with MRI. Results: Of the 19 patients, sixteen (84.2%) of them had positive finding in bone scan, fifteen (78.9%) had MRI of the spine. While of the thirteen patients who had positive finding in MRI, seven (53.8%) had more positive finding in thorcolumbosacral MRI than in bone scan. Conclusions: 99m-Tc MDP bone scan is a sensitive but insufficient method for detecting bone lesions in MM.

Teaching Point: Cemento-ossifying fibromas are rare, benign tumours that are mostly found in the tooth-bearing areas of the mandible or maxilla and can be seen on conebeam computed tomography. [ABSTRACT FROM AUTHOR]

Sarcoidosis is a multi-systemic disease characterized by non-caseating granulomas. Bone involvement initially considered as rare and described as a peripheral osteitis of the hands and feet, has recently been reported on the axial skeleton. We report 4 clinical observations of sarcoidosis (3 women, 1 man) with axial bone involvement located to the spine (n = 4), pelvic bone (n = 2), scapular bone (n = 2), sternum (n = 1), mandible (n = 1). Sarcoidosis was already diagnosed in 3 cases. Bone pain was the main symptom, related in 3 cases. Magnetic resonance imaging appeared to be the best imaging test Histological bone analysis revealed typical granulomatous lesions (n = 2). Treatment included corticosteroids (n = 4), hydroxychloroquine (n = 2), and methotrexate (n = 2), with a good efficacy on bone pain in symptomatic patients. These 4 cases, as well as recent literature, illustrate bone involvement of sarcoidosis on the axial skeleton. It is symptomatic in around 50% of cases but may be a source of significant disability. Differential diagnosis with neoplasm may require bone histological analysis. This condition appears to be responsive to usual treatments for sarcoidosis. [ABSTRACT FROM AUTHOR]

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