Analyses of the clinical characteristics of 49 cases of malignancy with multiple bone lesions as the first manifestation

Objective To investigate the clinical features of several cases of malignancy with multiple bone lesions as the first manifestation.Methods Forty-nine cases of malignancy with multiple bone lesions as the first manifestation were retrospectively analyzed from May 2018 to July 2019.All patients complained of“pain at the site of bone lesion”upon admission.Baseline patient information,such as age,gender,location of bone lesions,etiology,diagnosis method,time of onset was collected.Results The median age of the patients was 56 years old,of which 83.7%(41/49)were aged≥50 years.The median time of onset was 2 months.Among the cases,40 were confirmed as solid tumor bone metastasis,whereas the remaining 9 cases as hematological system tumor.Lung cancer and multiple myeloma were the main tumor types,accounting for 40.8%(20/49)and 16.3%(8/49),respectively.Other common causes were seven cases of cancer affecting the digestive system(three cases of liver cancer,three cases of gastric cancer,and one case of esophageal cancer),as well as seven cases of unknown primary cancer.Half of the solid tumors had only multiple bone metastases but no other distant metastasis.Conclusion Multiple bone lesions accompanied by pain may be the first clinical manifestation in various malignant tumors.The common tumor types were lung cancer,multiple myeloma,and digestive system tumor.It is more common in people aged 50 years and older.Multiple bone lesions might be the only metastasis site of some solid tumors,and its mechanism needs further investigation.

Florid reactive periostitis ossificans of the humerus: Case report and differential diagnosis of periosteal lesions of long bones

A case of florid reactive periostitis ossificans(RPO) arising in a long bone is presented. This is a rare bone proliferation with a pronounced periosteal reaction. Less than 100 cases have been described in the literature with far fewer outside the bones of the hand, feet, fingers, and toes. Although the etiology is unknown, a relationship to preceding trauma is suggested. The imaging and histologic features show an overlap with other bone lesions including bizarre parosteal osteochondromatous proliferation, subungual exostosis, and malignant surface tumors of bone and cartilage which include, periosteal and parosteal osteosarcoma. It is important to recognize the clinical presentation and diagnostic features of RPO as a benign entity so that it is not mistaken for a more aggressive neoplasm. We present a case of a right distal humeral lesion that on histopathological review revealed florid RPO. This diagnosis was not suspected on imaging studies, but was made on open biopsy of the mass. The patient remains disease free, years postoperatively. In addition to presenting this unique case report, we review the pertinent literature, and offer a differential diagnosis and treatment strategy for its management.

Establishing proof of concept:Platelet-rich plasma and bone marrow aspirate concentrate may improve cartilage repair following surgical treatment for osteochondral lesions of the talus

Osteochondral lesions of the talus are common injuries in the athletic patient. They present a challenging clinical problem as cartilage has a poor potential for healing. Current surgical treatments consist of reparative(microfracture) or replacement(autologous osteochondral graft) strategies and demonstrate good clinical outcomes at the short and medium term follow-up. Radiological findings and second-look arthroscopy however, indicate possible poor cartilage repair with evidence of fibrous infill and fissuring of the regenerative tissue following microfracture. Longer-term follow-up echoes these findings as it demonstrates a decline in clinical outcome. The nature of the cartilage repair that occurs for an osteochondral graft to become integrated with the native surround tissue is also of concern. Studies have shown evidence of poor cartilage integration,with chondrocyte death at the periphery of the graft, possibly causing cyst formation due to synovial fluid ingress. Biological adjuncts, in the form of platelet-rich plasma(PRP) and bone marrow aspirate concentrate(BMAC), have been investigated with regard to their potential in improving cartilage repair in both in vitro and in vitro settings. The in vitro literature indicates that these biological adjuncts may increase chondrocyte proliferation as well as synthetic capability, while limiting the catabolic effects of an inflammatory joint environment. These findings have been extrapolated to in vitro animal models, with results showing that both PRP and BMAC improve cartilage repair. The basic science literature therefore establishes the proof of concept that biological adjuncts may improve cartilage repair when used in conjunction with reparative and replacement treatment strategies for osteochondral lesions of the talus.

Preventive effects of autologous bone marrow mononuclear cell implantation on intrahepatic ischemic-type biliary lesion in rabbits

BACKGROUND: The ischemic-type biliary lesion (ITBL) is one of the most serious biliary complications of liver transplantation. This study aimed to investigate the effects of autologous bone marrow mononuclear cell (BM-MNC) implantation on neovascularization and the prevention of intrahepatic ITBL in a rabbit model. METHODS: The rabbits were divided into control, experimental model, and cell implantation groups, with 10 in each group. The model of intrahepatic ITBL was established by clamping the hepatic artery and common bile duct. Autologous BM-MNCs were isolated from the tibial plateau by density gradient centrifugation and were implanted through the common hepatic artery. Changes in such biochemical markers as aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, gamma-glutamyltranspeptidase, total bilirubin and direct bilirubin were measured. Four weeks after operation, cholangiography, histopathological manifestations, differentiation of BM-MNCs, microvessel density and the expression of vascular endothelial growth factor were assessed. RESULTS: Compared with the experimental model group, the BM-MNC implantation group showed superiority in the time to recover normal biochemistry. The microvessel density and vascular endothelial growth factor expression of the implantation group were significantly higher than those of the control and experimental model groups. The ITBL in the experimental model group was more severe than that in the implantation group and fewer new capillary blood vessels occurred around it. CONCLUSIONS: Implanted autologous BM-MNCs can differentiate into vascular endothelial cells, promote neovascularization and improve the blood supply to the ischemic bile duct, and this provides a new way to diminish or prevent intrahepatic ITBL after liver transplantation. (Hepatobiliary Pancreat Dis Int 2010; 9:593-599)

Bone lesions in recurrent glucagonoma: A case report and review of literature

Glucagonomas are rare neuroendocrine tumors that arise from cells of the pancreatic islets. Most of them are malignant and usually present as metastatic disease. Sites most commonly involved in metastases are the liver and regional lymph nodes. Bone metastases are rare events and only a few cases have been reported in the literature. We present the case of a 53-year-old male with a medical history of recurrent non-functioning glucagonoma. He presented 17 years after the initial diagnosis with new blastic bone lesions involving the T1 vertebra and the sacrum. Diagnostic steps and medical management in metastatic glucagonoma are also reviewed.

U-Net Based Dual-Pooling Segmentation of Bone Metastases in Thoracic SPECT Bone Scintigrams

In order to enhance the performance of the CNN-based segmentation models for bone metastases, this study proposes a segmentation method that integrates dual-pooling, DAC, and RMP modules. The network consists of distinct feature encoding and decoding stages, with dual-pooling modules employed in encoding stages to maintain the background information needed for bone scintigrams diagnosis. Both the DAC and RMP modules are utilized in the bottleneck layer to address the multi-scale problem of metastatic lesions. Experimental evaluations on 306 clinical SPECT data have demonstrated that the proposed method showcases a substantial improvement in both DSC and Recall scores by 3.28% and 6.55% compared the baseline. Exhaustive case studies illustrate the superiority of the methodology.

Specific bone region localization of osteolytic versus osteoblastic lesions in a patient-derived xenograft model of bone metastatic prostate cancer

Objective:Bone metastasis occurs in up to 90%of men with advanced prostate cancer and leads to fractures,severe pain and therapy-resistance.Bone metastases induce a spectrum of types of bone lesions which can respond differently to therapy even within individual prostate cancer patients.Thus,the special environment of the bone makes the disease more complicated and incurable.A model in which bone lesions are reproducibly induced that mirrors the complexity seen in patients would be invaluable for pre-clinical testing of novel treatments.The microstructural changes in the femurs of mice implanted with PCSD1,a new patient-derived xenograft from a surgical prostate cancer bone metastasis specimen,were determined.Methods:Quantitative micro-computed tomography(micro-CT)and histological analyses were performed to evaluate the effects of direct injection of PCSD1 cells or media alone(Control)into the right femurs of Rag2
/
gc
/
male mice.Results:Bone lesions formed only in femurs of mice injected with PCSD1 cells.Bone volume(BV)was significantly decreased at the proximal and distal ends of the femurs(p<0.01)whereas BV(p<0.05)and bone shaft diameter(p<0.01)were significantly increased along the femur shaft.Conclusion:PCSD1 cells reproducibly induced bone loss leading to osteolytic lesions at the ends of the femur,and,in contrast,induced aberrant bone formation leading to osteoblastic lesions along the femur shaft.Therefore,the interaction of PCSD1 cells with different bone region-specific microenvironments specified the type of bone lesion.Our approach can be used to determine if different bone regions support more therapy resistant tumor growth,thus,requiring novel treatments.

Comparisons between glucose analogue 2-deoxy-2-(^(18)F)fluoro-D-glucose and ^(18)F-sodium fluoride positron emission tomography/computed tomography in breast cancer patients with bone lesions

AIM: To compare 2-deoxy-2-(18F)fluoro-D-glucose(18F-FDG) and 18F-sodium (18F-NaF) positron emission tomography/computed tomography (PET/CT) accuracy in breast cancer patients with clinically/radiologically suspected or known bone metastases.METHODS: A total of 45 consecutive patients with breast cancer and the presence or clinical/biochemical or radiological suspicion of bone metastatic disease underwent 18F-FDG and 18F-fluoride PET/CT. Imaging results were compared with histopathology when available, or clinical and radiological follow-up of at least 1 year. For each technique we calculated: Sensitivity (Se), specificity (Sp), overall accuracy, positive and negative predictive values, error rate, and Youden’s index. McNemar’s χ2 test was used to test the difference in sensitivity and specificity between the two diagnostic methods. All analyses were computed on a patient basis, and then on a lesion basis, with consideration ofthe density of independent lesions on the co-registered CT (sclerotic, lytic, mixed, no-lesions) and the divergent site of disease (skull, spine, ribs, extremities, pelvis). The impact of adding 18F-NaF PET/CT to the work-up of patients was also measured in terms of change in their management due to 18F-NaF PET/CT findings.RESULTS: The two imaging methods of 18F-FDG and 18F-fluoride PET/CT were significantly different at the patient-based analysis: Accuracy was 86.7% and 84.4%, respectively (McNemar’s χ2 = 6.23, df = 1, P = 0.01). Overall, 244 bone lesions were detected in our analysis. The overall accuracy of the two methods was significantly different at lesion-based analysis (McNemar’s χ2 = 93.4, df = 1, P < 0.0001). In the lesion density-based and site-based analysis, 18F-FDG PET/CT provided more accurate results in the detection of CT-negative metastasis (P < 0.002) and vertebral localizations (P < 0.002); 18F-NaF PET/CT was more accurate in detecting sclerotic (P < 0.005) and rib lesions (P < 0.04). 18F-NaF PET/CT led to a change of management in 3 of the 45 patients (6.6%) by revealing findings that were not detected at 18F-FDG PET/CT.CONCLUSION: 18F-FDG PET/CT is a reliable imaging tool in the detection of bone metastasis in most cases, with a diagnostic accuracy that is slightly, but significantly, superior to that of 18F-NaF PET/CT in the general population of breast cancer patients. However, the extremely high sensitivity of 18F-fluoride PET/CT can exploit its diagnostic potential in specific clinical settings (i.e., small CT-evident sclerotic lesions, high clinical suspicious of relapse, and negative 18F-FDG PET and conventional imaging).

Systematic review of bone marrow stimulation for osteochondral lesion of talus-evaluation for level and quality of clinical studies

AIM To clarify the quality of the studies indicating lesion size and/or containment as prognostic indicators of bone marrow stimulation(BMS) for osteochondral lesions of the talus(OLT). METHODS Two reviewers searched the Pub Med/MEDLINE and EMBASE databases using specific terms on March 2015 in accordance with the Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines. Predetermined variables were extracted for all the included studies. Level of evidence(LOE) was determined using previously published criteria by the Journal of Bone and Joint Surgery and methodological quality of evidence (MQOE) was evaluated using the Modified Coleman Methodology Score. RESULTS This review included 22 studies. Overall, 21 of the 22(95.5%) included studies were level Ⅳ or level Ⅲ evidences. The remaining study was a level Ⅱ evidence. MQOE analysis revealed 14 of the 22(63.6%) included studies having fair quality, 7(31.8%) studies having poor quality and only 1 study having excellent quality. CONCLUSION The evidence supporting the use of lesion size and containment as prognostic indicators of BMS for OLTs has been shown to be of low quality.

Effects of Early Weightbearing on Microfracture Treatment of Osteochondral Lesions of Talus with Subchondral Bone Defects

When subchondral bone defects are present in osteochondral lesions of the talus(OCLT),it is inconclusive whether to allow early weightbearing after microfracture treatment because of the lack of effective support of the newly-formed fibrocartilage.After performing arthroscopic debridement and microfracture treatment on OCLT patients with subchondral bone defects,we allowed patients to have an early postoperative weightbearing exercise to observe their clinical outcome.Forty-two OCLT patients with subchondral bone defects were analyzed.Patients were randomly divided into two groups with 21 patients in each group.After arthroscopic debridement and microfracture treatment,group A was allowed to have early partial weightbearing while weightbearing was delayed in group B.Visual analogue scale(VAS)was used to evaluate joint pain before and after surgery.American Orthopaedic Foot and Ankle Society(AOFAS)anklc-hindfoot score was used to evaluate joint function.Tegner activity scale was used to assess patient's exercise level.The AOFAS ankle-hindfoot score in group A increased from 54.4 to 87.6,and that in group B increased from 54.9 to 87.3.The VAS score in group A decreased from 6.5 to 2.2,and that in group B decreased from 6.4 to 2.3.The Tegner activity scale increased from 2.6 to 4.4 in group A,and that in group B increased from 2.6 to 3.9.There was significant difference in the Tegner activity scale between group A and group B(P<0.05).It was suggested that when performing microfracture treatmenf on OCLT patients with subchondral bone defects,early postoperative weightbearing may achieve similar clinical outcomes as delayed weightbearing,and patients may be better able to return to sports.

Local Adjuvants in Surgical Management of Bone Lesions

One of the most common methods for surgical treatment of bone metastasis is curettage. Local adjuvants are used to improve the effect of curettage in local cancer surgery and they may exerted their effects either chemically either physically;in orthopaedic oncology the most common are phenol, liquid nitrogen, laser, cement and argon beam coagulation. The purpose of this article is to review the main characteristics of the most common chemical and physical agents used in bone oncology, emphasizing the toxic effects of some of them, especially phenol and liquid nitrogen.

Histological Findings of Bone Marrow Lesions on Magnetic Resonance Images in Patients with Varus Knee Osteoarthritis

Bone marrow lesions (BMLs) on magnetic resonance (MR) images in knee osteoarthritis patients are considered to predict the severity and progression of the disease. We evaluated the histological findings of BMLs on MR images of the subchondral area of the medial femoral condyle in varus osteoarthritic knees. In 24 patients with varus knee osteoarthritis who underwent total knee arthroplasty (TKA), sagittal T1- and T2-weighted MR images of the affected knee were acquired before TKA. During TKA, resected bone pieces from the distal medial femoral condyle were obtained. Sagittal specimens obtained from the center of the bone pieces were histologically examined. Twenty patients had BMLs. Histological findings of BMLs in the subchondral area showed various features, such as fibrovascular tissue, cyst formation, active bone remodeling with bone formation and bone resorption, and hyaline cartilage. BMLs were not found in four patients;histological findings of these patients showed normal bone marrow tissue with normal-thickness trabeculae. Subchondral bony end plate in knees with BMLs was usually thin or destroyed, while that without BMLs was thick or normal. The condition of the subchondral bony end plate would explain the differences in the severity and progression between patients with or without BMLs.

Scapular bone grafting with allograft pin fixation for repair of bony Bankart lesions: A biomechanical study

BACKGROUND Severe bony Bankart lesions are a difficult challenge in clinical treatment and research.The current treatment methods consist mostly of Latarjet-Bristow surgery and its modified procedures.While good results have been achieved,there are also complications such as coracoid fracture,bone graft displacement,and vascular and nerve injury.AIM To analyze the techniques and biomechanical properties of transversely fixing a bone block from the scapular spine using bone allograft pins with suture threads to repair bony Bankart lesions.METHODS Fresh human shoulder joint specimens and a cadaver specimen model for scapular bone grafting with allograft pin fixation for repair of bony Bankart lesions were used.When the humeral rotation angles were 0°,30°,60°and 90°,and the axial loads were 30 N,40 N,and 50 N,the humerus displacement was studied by biomechanical experiments.RESULTS When the angle of external rotation of the humerus was 0°,30°,60°,and 90°,with axial loads of 30 N,40 N,and 50 N,the data of the normal control group,allograft pin repair group,and titanium alloy hollow screw repair group were compared with each other by the q-test,which showed that there were no statistically differences among the three groups(P>0.05).CONCLUSION The joints repaired with bone block from the scapular spine transversely fixed with allograft bony pins to repair bony Bankart lesions show good mechanical stability.The bone block has similar properties to normal glenohumeral joints in terms of biomechanical stability.

Fracture risk assessment in children with benign bone lesions of long bones

BACKGROUND Fracture risk assessment in children with benign bone lesions of long bones remains poorly investigated.AIM To investigate the risk factors for pathological fracture in children with benign bone lesions and to propose a modified scoring system for quantitative analysis of the pathologic fracture risk.METHODS We retrospectively reviewed 96 pediatric patients with benign bone lesions.We compared radiographic and clinical features between 40 patients who had fractures through a benign bone lesion and 56 who had no fracture.Information including histological diagnosis,anatomical site,radiographic appearance,severity of pain,and lesion size was recorded for the patients.A modified scoring system was proposed to predict the risk of fracture.RESULTS The univariate comparisons showed a significant difference between the fracture and non-fracture groups in terms of lesion type,pain,lesion-to-bone width,and axial cortical involvement of the patients(P<0.05).Lesion type,pain,lesion-tobone width,and axial cortical involvement were independently correlated with an increased risk of fracture.The mean score of the fracture group was 7.89,whereas the mean score of the non-fracture group was 6.01.The optimum cut-off value of the score to predict pathological fracture was 7.The scoring system had a sensitivity of 70%and a specificity of 80%for detecting patients with fractures.The Youden index was 0.5,which was the maximum value.The area under the receiver operator characteristic was 0.814.CONCLUSION Lesion type,pain,lesion-to-bone width,and axial cortical involvement are risk factors for pathological fracture.The modified scoring system can provide evidence for clinical decision-making in children with benign bone lesions.A bone lesion with a total score>7 indicates a high risk of a pathologic fracture and is an indication for prophylactic internal fixation.

Non-secretory multiple myeloma with lytic bone lesions about a new observation

Non-secretory myeloma is a rare variety of multiple myeloma. Classical techniques of chronic secretion’s research don’t find any immunoglobulin monoclonal peak in the patient’s blood. Lytic bone lesions are rare in this type of myeloma. We report the case of a patient in whom we confirmed multiple myeloma by bone marrow aspiration and we have classified stage III of Durie and Salmon in view of hypercalcemia, anemia, and lytic lesions observed. However, we could not isolate a secretion of monoclonal immunoglobulin in blood but urinary secretion was evident by proteinuria and urinary light chains. The radiographs of our patient found diffuse osteolysis and practice of sternal puncture confirmed multiple myeloma. Our case is original because of rarity on non secretory myeloma particularly with diffuse osteolytic lesion.

Enchondromas of Long Bones and Other Skeletal Lesions Found Incidentally Need Critical Evaluation, But Rarely Systematic Follow-Up

Purpose: Incidental bone lesions are a challenge for the specialist, who has to give recommendations for further management. This review of our cases will assist in the decision whether the lesion can be “neglected”, needs further active follow-up or direct initiation of treatment. Patients and Methods: 153 cases of incidental bone findings were presented to our musculoskeletal tumor service for evaluation from July 2008 through June 2021. 73 of them were cartilaginous tumors and 63 of these were diagnosed as enchondroma of a long bone based on X-Ray and MRI. Results: Follow-up imaging of the enchondroma patients was available for 35 patients at 1 to 13 years (mean 4.3 y), with no change in size except for one femoral diaphyseal enchondroma with increasing diameter from age 18 to 20 years. 14 additional patients answered written contact stating that they remained asymptomatic at 2 to 12 years (mean 5.6 y). None of the patients has been reported to the Swiss Confoederation Cancer Registry to have developed malignancy. Among the 10 other cartilaginous tumors were one chondrosarcoma grade II exhibiting different imaging, 3 non-long-bone localizations (pelvis, scapula and rib), 2 Ollier-type enchondromas, and 2 osteochondromas. Incidental findings other than cartilaginous tumors were fibrous dysplasia (n = 31), non-ossifying fibroma (n = 31) and 18 other “sporadic” entities. Conclusions: Incidentally found enchondromas not exhibiting aggressive features need no systematic follow-up and patients can be “discharged” with the advice to present, if symptoms would develop. This also applies to fibrous dysplasia and the other sporadic lesions. 6 cases with other diagnoses needed specific treatment.

Reliability and sensitivity to change of IW-TSE versus DESS magnetic resonance imaging sequences in the assessment of bone marrow lesions in knee osteoarthritis patients: Longitudinal data from the Osteoarthritis Initiative (OAI) cohort

Background: Bone marrow lesions (BMLs) are associated with osteoarthritis (OA). We assessed the performance of two commonly used MRI sequences, IW-TSE and DESS, for reliability in the detection of BMLs and sensitivity to estimate change over time. We suggested that the IW-TSE would demonstrate higher sensitivity to change than DESS in the assessment of BML prevalence and change over time. This study was performed using a subset of the Osteoarthritis Initiative (OAI) cohort. Methods: A sub-group of 144 patients was selected from the OAI progression cohort who all had IW-TSE and DESS MRI acquisitions at baseline and 24 months. BMLs were assessed using a semi-quantitative scale in the global knee, medial and lateral compartments, and subregions. Intra-reader reliability was assessed on a subset of 51 patients. Results: Intra-reader reliability was substantial for the global knee ≥ 0.64, medial ≥ 0.70, and lateral ≥ 0.63 compartments for IW-TSE and DESS. The prevalence of BML detected at baseline was only slightly greater for IW-TSE compared to DESS. The mean BML score at baseline was significantly higher (p ≤ 0.006) for the IW-TSE than the DESS. However, mean change at 24 months was similar for both sequences for all regions except the medial compartment (p = 0.034) and medial femur (p = 0.015) where they were significantly higher for DESS than IW-TSE. Moreover, the prevalence of BML change at 24 months was similar in all regions except the global knee (p = 0.047) and the lateral tibial plateau (p = 0.031). Conclusion: This study does not suggest superior sensitivity to change of one sequence over the other for almost all the regions. The only difference is a higher BML mean change over time detected by the DESS sequence in the medial compartment and femur. These data bring into perspective that both sequences seem equivalent regarding their use for the assessment of BML in clinical trials.

Skeletal cystic angiomatosis:A rare cause of unilateral lytic bone lesions

Cystic angiomatosis is a rare, benign, multifocal disorder of bone and viscera. Angiomatous deposits result in bone lysis and organ dysfunction. Bony cystic lesions occur in the axial and proximal appendicular skeleton. Lesions may cause bone pain or pathological fracture. Diagnosis is difficult, of exclusion and demands a biopsy. The prognosis varies upon whether the lesions are solely skeletal or there is visceral involvement. A 71-year-old man reports increasing symptoms of painful swelling in the right thoracic wall for over a month. The swelling was bony hard in consistency. Except for his bony swelling, the patient’s physical examination was within normal limits, as were all his laboratory studies. X-ray imagery showed multicystic expansive lytic areas involving the right ribs. Computerized tomography, magnetic resonance imagery and gallium bone scan revealed lytic lesions of multiple right ribs, and cervical, dorsal, lumbar and sacrum iliac spine. A right rib biopsy has shown a cystic formation with endothelial walls. Five years later, the patient remained stable, with no clinical, laboratory or imagilogic progression of disease and without visceral involvement. This case is presented in his rarity and differential diagnosis challenge.

Multiple myeloma mesenchymal stromal cells: Contribution to myeloma bone disease and therapeutics

Multiple myeloma is a hematological malignancy inwhich clonal plasma cells proliferate and accumulate within the bone marrow. The presence of osteolytic le-sions due to increased osteoclast(OC) activity and sup-pressed osteoblast(OB) function is characteristic of the disease. The bone marrow mesenchymal stromal cells(MSCs) play a critical role in multiple myeloma patho-physiology, greatly promoting the growth, survival, drug resistance and migration of myeloma cells. Here, we specifically discuss on the relative contribution of MSCs to the pathophysiology of osteolytic lesions in light of the current knowledge of the biology of my-eloma bone disease(MBD), together with the reported genomic, functional and gene expression differences between MSCs derived from myeloma patients(pMSCs) and their healthy counterparts(dMSCs). Being MSCs the progenitors of OBs, pMSCs primarily contribute to the pathogenesis of MBD because of their reduced osteogenic potential consequence of multiple OB inhibi-tory factors and direct interactions with myeloma cells in the bone marrow. Importantly, pMSCs also readily contribute to MBD by promoting OC formation and ac-tivity at various levels(i.e., increasing RANKL to OPG expression, augmenting secretion of activin A, uncou-pling ephrinB2-EphB4 signaling, and through augment-ed production of Wnt5a), thus further contributing to OB/OC uncoupling in osteolytic lesions. In this review, we also look over main signaling pathways involved in the osteogenic differentiation of MSCs and/or OB activity, highlighting amenable therapeutic targets; in parallel, the reported activity of bone-anabolic agents(at preclinical or clinical stage) targeting those signaling pathways is commented.

Clinical application of concentrated bone marrow aspirate in orthopaedics:A systematic review

AIM To examine the evidence behind the use of concentrated bone marrow aspirate(c BMA) in cartilage, bone, and tendon repair; establish proof of concept for the use of cB MA in these biologic environments; and provide the level and quality of evidence substantiating the use of cB MA in the clinical setting.METHODS We conducted a systematic review according to PRISMA guidelines. EMBASE, MEDLINE, and Web of Knowledge databases were screened for the use of cB MA in the repair of cartilage, bone, and tendon repair. We extracted data on tissue type, cB MA preparation, cB MA concentration, study methods, outcomes, and level of evidence and reported the results in tables and text.RESULTS A total of 36 studies met inclusion/exclusion criteria and were included in this review. Thirty-one of 36(86%) studies reported the method of centrifugation and preparation of cB MA with 15(42%) studies reporting either a cell concentration or an increase from baseline. Variation of c BMA application was seen amongst the studies evaluated. Twenty-one of 36(58%) were level of evidence Ⅳ, 12/36(33%) were level of evidence Ⅲ, and 3/36(8%) were level of evidence Ⅱ. Studies evaluated full thickness chondral lesions(7 studies), osteochondral lesions(10 studies), osteoarthritis(5 studies), nonunion or fracture(9 studies), or tendon injuries(5 studies). Significant clinical improvement with the presence of hyaline-like values and lower incidence of fibrocartilage on T2 mapping was found in patients receiving cB MA in the treatment of cartilaginous lesions. Bone consolidation and time to bone union was improved in patients receiving cB MA. Enhanced healingrates, improved quality of the repair surface on ultrasound and magnetic resonance imaging, and a decreased risk of re-rupture was demonstrated in patients receiving cB MA as an adjunctive treatment in tendon repair. CONCLUSION The current literature demonstrates the potential benefits of utilizing c BMA for the repair of cartilaginous lesions, bony defects, and tendon injuries in the clinical setting. This study also demonstrates discrepancies between the literature with regards to various methods of centrifugation, variable cell count concentrations, and lack of standardized outcome measures. Future studies should attempt to examine the integral factors necessary for tissue regeneration and renewal including stem cells, growth factors and a biologic scaffold.