Malignant Bone Disease Research Articles

Surgical Profile of Osteosarcoma Patients in a Tertiary Referral Hospital in Surabaya, Indonesia

Osteosarcoma is a rare malignant bone disease with unclear etiology. It is primarily a disease of childhood with rapid bone growth in periods of rapid bone proliferation [such as in puberty]. Before the 1970s, prognosis for this malignancy is very grim with the only available form of treatment are limb ablation [amputation]. The advent of modern chemotherapy, in addition to the development of modern limb salvage surgery [LSS] techniques, mortality has decreased and quality of life of surviors have increased. Indonesia is a developing country with unequal distribution of adequate health facilities. Studies have shown that unlike western countries, most osteosarcoma patients in Indonesia are still treated with limb ablation procedures. A retrospective descriptive study is done on Dr. Soetomo General Hospital to discover the surgical profile of patients undergoing chemotherapy during the period of 2014-2020. Results have shown that the majority [26] underwent amputation, 17 underwent no surgical treatment, and the rest [9] LSS. The results of this research shows that the clinical reality of developing nations like Indonesia is still far from the ideal clinical situation in developed western nations where these studies originate.

Selenoprotein W engages in overactive osteoclast differentiation in multiple myeloma

BackgroundPatients with multiple myeloma exhibit malignant osteolytic bone disease due to excessive osteoclast formation and function. We recently identified that osteoclastogenic stimulator selenoprotein W (SELENOW) is upregulated via ERK signaling and downregulated via p38 signaling during receptor activator of nuclear factor (NF)-κΒ ligand (RANKL)-induced osteoclast differentiation. In the intrinsic physiological process, RANKL-induced downregulation of SELENOW maintains proper osteoclast differentiation; in contrast, forced overexpression of SELENOW leads to overactive osteoclast formation and function.Methods and resultsWe observed that SELENOW is highly expressed in multiple myeloma-derived peripheral blood mononuclear cells (PBMCs) and mature osteoclasts when compared to healthy controls. Also, the level of tumor necrosis factor alpha (TNFα), a pathological osteoclastogenic factor, is increased in the PBMCs and serum of patients with multiple myeloma. ERK activation by TNFα was more marked and sustained than that by RANKL, allowing SELENOW upregulation. Excessive expression of SELENOW in osteoclast progenitors and mature osteoclasts derived from multiple myeloma facilitated efficient nuclear translocation of osteoclastogenic transcription factors NF-κB and NFATc1, which are favorable for osteoclast formation.ConclusionOur findings suggest a possibility that feedforward signaling of osteoclastogenic SELENOW by TNFα derived from multiple myeloma induces overactive osteoclast differentiation, leading to bone loss during multiple myeloma.

An Injectable Hydrogel System with Mild Photothermal Effects Combined with Ion Release for Osteosarcoma‐Related Bone Defect Repair

AbstractOsteosarcoma, a common invasive malignant bone disease, presents therapeutic challenges due to the persistent problem of incomplete resection during surgical treatment. This often results in postoperative tumor recurrence and metastasis, and large‐scale bone defects are difficult to self‐repair, seriously affecting patient health. In this study, a dual‐ion doped organic‐inorganic composited SOH1(CP)1 injectable hydrogel system is successfully designed and constructed. This system consists of sericin protein grafted with hydrazide bonds, oxidized chondroitin sulfate, Se and Mg co‐doped HAp nanorods, and polydopamine‐coated CaO2 nanospheres. The system displays strong anti‐tumor activity due to its mild photothermal effects combined with the chemotherapeutic efficacy of SeO32−. Because the degradation behavior of hydrogel matches the bone repair cycle, including the nutritional support of hydrogel skeleton degradation products to promote bone cell proliferation, and the positive regulation of Ca2+, Mg2+, and PO43− released via the degradation of inorganic nanoparticles to promote bone differentiation, the system shows excellent bone defect repair efficacy. Importantly, this system achieves 100% tumor inhibition after 18 days, while ensuring complete bone repair after 12 weeks. Hence, the SOH1(CP)1 injectable hydrogel system, which displays both high anti‐osteosarcoma efficacy and strong bone repair properties, can serve as a new tool for osteosarcoma‐related bone defect repair.

Cancer treatment-induced bone loss.

Cancer treatment-induced bone loss (CTBL) is associated with anti-tumor treatments, including endocrine therapies, chemotherapeutic treatments, radiotherapy, glucocorticoids, and tyrosine kinase inhibitors. Osteoporosis, characterized by the loss of bone mass, can increase the risk of fractures, leading to mortality and long-term disability, even after cancer remission. Cancer and osteoporosis have marked clinical and pathogenetic similarities. Both have a multifactorial etiology, affect the geriatric population, and markedly influence quality of life. Lifestyle management, including calcium and vitamin D supplementation, is recommended but the supporting evidence is limited. Oral and injectable bisphosphonates are effective for osteoporosis and malignant bone disease. Bisphosphonates increase bone mineral density (BMD) in patients with CTBL. Denosumab is also used in the management of CTBL; in clinical trials, it improved BMD and reduced the risk of fracture. Currently, there are no bone anabolic therapies for patients with cancer. Appropriate therapies are necessary to maintain optimal bone health, particularly in patients at heightened risk.

Deep learning assisted atlas-based delineation of the skeleton from Whole-Body Diffusion Weighted MRI in patients with malignant bone disease

BackgroundWhole-Body Diffusion Weighted MRI (WBDWI) can provide a basis for quantifying disease volume and apparent diffusion coefficient (ADC) to aid disease staging and response assessment of metastatic bone disease. In this study, we develop atlas-based registration assisted by two AI-based models (i) body-region classification for automatic identification of legs, pelvis, lumbar/thoracic/cervical spine and head, and (ii) automated spinal cord segmentation, to automatically delineate the whole skeleton on WBDWI. MethodsTraining and validation of AI-based models were performed on 40 patients (32:8 split) with confirmed Advanced Prostate Cancer (APC) who underwent baseline and after treatment WBDWI scans. Consequent atlas-based skeleton segmentation accuracy was validated using leave-one-out cross-validation in a cohort of 15 patients with Multiple Myeloma (MM). ResultsAtlas-based registration in combination with AI-based models demonstrated higher performance in segmenting the spinal column when compared with the traditional techniques (average dice score for the lumbar, thoracic and cervical spine of 0.77/0.78/0.68 compared to 0.71/0.69/0.51 from the conventional method, respectively). Similar performances were observed for long bones, pelvic girdle and ribcage (average dice score of 0.65/0.7/0.47, respectively). Our approach demonstrated lower relative median ADC and skeleton volume difference between estimation and ground truth compared to conventional atlas-based methods (average relative median ADC and skeleton volume difference of 10.3/2.1% compared to 13/2.7%, respectively). ConclusionAI-augmented atlas-based registration substantially improves the accuracy of derived skeletal segmentations from WBDWI compared with traditional atlas-based registration.

The diagnostic roles of fused <sup>18</sup>F-fluorodeoxyglucose positron emission tomography/computed tomography and bone scintigraphy in children and young adults with bone sarcomas: a systematic review and meta-analysis

Osteosarcoma and Ewing sarcoma are the most common primary malignant bone diseases in children. An accurate diagnosis and staging of these tumors play a pivotal role in choosing the optimal treatment and predicting outcomes. In recent years, fused 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography/computed tomography (PET/CT) has been increasingly used in the diagnosis of bone sarcomas. It is frequently applied in conjunction with, or as a replacement for bone scintigraphy (BS), in order to determine the extent of the disease. However, the questions on the diagnostic significance of these methods and the choice of the most effective approach to the management of children with bone sarcomas still remain unanswered. We conducted a systematic review and meta-analysis to compare the diagnostic roles of 18F-FDG PET/CT and BS in staging and restaging of bone sarcomas in children and young adults. The study was carried out in accordance with the Cochrane PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Two independent researchers looked for prospective and retrospective studies evaluating the sensitivity and specificity of 18F-FDG PET/CT and BS in staging and restaging of bone sarcomas in children and young adults, published over the last 15 years. The quality of the included studies was assessed using the QUADAS-2 tool. Summary Receiver Operating Characteristic curves were calculated using STATA 17 software packages and the RevMan 5.3 tool to evaluate the overall diagnostic value of PET/CT and BS. The certainty of evidence was evaluated using the GRADE system. This systematic review and meta-analysis included 8 studies (530 patients with bone sarcomas). These studies used 11 patient cohorts (osteosarcoma: 5 cohorts, 305 patients; Ewing sarcoma: 6 cohorts, 225 patients). We discovered that 18F-FDG PET/CT had high sensitivity in staging and restaging of bone sarcomas (94% (95% confidence interval (CI) 89–97)). On the other hand, BS demonstrated lower sensitivity (69% (95% CI 58–79), the mean difference being 25% (95% CI 18.89–31.00), p < 0.001). At the same time, the specificity of 18F-FDG PET/CT and the specificity of BS were found to be comparable (96% (95% CI 83–99) and 92% (95% CI 82–97) respectively, p = 0.15). All the results were confirmed in a subgroup analysis of patients with osteosarcoma and Ewing sarcoma. The results of our systematic review and meta-analysis lead us to conclude that 18F-FDG PET/CT is a more sensitive method for staging and restaging of bone sarcomas in children and young adults, compared to BS. However, both methods have high specificity. Considering our findings, future clinical research in children with bone sarcomas should be aimed at further data collection to clarify the diagnostic roles of 18F-FDG PET/CT and BS both in children with osteosarcoma and in children with Ewing sarcoma, in order to identify clear indications and choose the best imaging method for detecting metastatic bone lesions, with the aim of developing an optimal diagnostic strategy.

OP82 Positron Emission Tomography Combined With Computed Tomography Using 18F-Sodium Fluoride

IntroductionPositron emission tomography combined with computed tomography (PET/CT) using 18F-sodium fluoride (18F-NaF) is used for functional imaging in diseases to detect abnormally altered osteogenic activity, such as benign and malignant bone diseases and inflammatory or traumatic changes in skeletal bones.MethodsA systematic search of literature using keywords in the MEDLINE database was conducted to identify literature on the clinical and cost effectiveness of using PET/CT with 18F-NaF-based radiopharmaceuticals in the diagnosis of bone and cartilage cancer. The search retrieved 323 publications. The analysis included 11 publications that met the selection criteria, including one meta-analysis and ten literature reviews.ResultsThe pooled sensitivity, specificity, diagnostic odds ratio (DOR) and area under the receiver operating characteristic curve of 18F-NaF-based PET/CT for the detection of bone metastases were 0.98 (95% confidence interval [CI]: 0.95, 0.99), 0.90 (95% CI: 0.86, 0.93), 123.2, and 0.97, respectively. 18F-NaF-based PET/CT was highly effective in detecting bone metastases during staging and restaging of patients with high-risk prostate cancer. The effectiveness of 18F-NaF-based PET/CT was superior to bone scintigraphy with technetium-99m and single-photon emission computed tomography (SPECT) and was comparable to diffusion-weighted imaging.ConclusionsPET/CT with 18F-NaF is a more accurate method of localizing and characterizing malignant bone lesions than SPECT. This method has improved clinical accuracy and provides greater convenience for patients and referring physicians. PET/CT with 18F-NaF in malignant neoplasms is a more specific, sensitive study than 18F-fluorodeoxyglucose PET/CT. These results were submitted to the Ministry of Health for a decision on the inclusion of 18F-NaF-based PET/CT in the state reimbursement system.

Analysis of complications and revisions after spine surgery in 270 multiple myeloma patients with spinal involvement

Background contextPatients with multiple myeloma (MM) are at increased risk of infections and suffer from poor bone quality due to their disseminated malignant bone disease. Therefore, postoperative complications may occur following surgical treatment of MM lesions.PurposeIn this study, we aimed to determine the incidence of postoperative complications and retreatments after spinal surgery in MM patients. Additionally, we sought to identify risk factors associated with complications and retreatments.Study designRetrospective cohort study.Patient sample.In total, 270 patients with MM who received surgical treatment for spinal involvement between 2008 and 2021 were included.Outcome measures.The incidence of perioperative complications within 6 weeks and reoperations within 2.5 years and individual odds ratios for factors associated with these complications and reoperations.MethodsData were collected through manual chart review. Hosmer and Lemeshow’s purposeful regression method was used to identify risk factors for complications and reoperations.ResultsThe median age of our cohort was 65 years (SD = 10.8), and 58% were male (n = 57). Intraoperative complications were present in 24 patients (8.9%). The overall 6-week complication rate after surgery was 35% (n = 95). The following variables were independently associated with 6-week complications: higher Genant grading of a present vertebral fracture (OR 1.41; 95% CI 1.04–1.95; p = .031), receiving intramuscular or intravenous steroids within a week prior to surgery (OR 3.97; 95% CI 1.79–9.06; p = .001), decompression surgery without fusion (OR 6.53; 95% CI 1.30–36.86; p = .026), higher creatinine levels (OR 2.18; 95% CI 1.19–5.60; p = .014), and lower calcium levels (OR 0.58; 95% CI 0.37–0.88; p = .013). A secondary surgery was indicated for 53 patients (20%), of which 13 (4.8%) took place within two weeks after the initial surgery. We additionally discovered factors associated with retreatments, which are elucidated within the manuscript.ConclusionThe goal of surgical treatment for MM bone disease is to enhance patient quality of life and reduce symptom burden. However, postoperative complication rates remain relatively high after spine surgery in patients with MM, likely attributable to both inherent characteristics of the disease and patient comorbidities. The risk for complications and secondary surgeries should be explored and a multidisciplinary approach is crucial.

Artificial intelligence-based analysis of whole-body bone scintigraphy: The quest for the optimal deep learning algorithm and comparison with human observer performance

PurposeWhole-body bone scintigraphy (WBS) is one of the most widely used modalities in diagnosing malignant bone diseases during the early stages. However, the procedure is time-consuming and requires vigour and experience. Moreover, interpretation of WBS scans in the early stages of the disorders might be challenging because the patterns often reflect normal appearance that is prone to subjective interpretation. To simplify the gruelling, subjective, and prone-to-error task of interpreting WBS scans, we developed deep learning (DL) models to automate two major analyses, namely (i) classification of scans into normal and abnormal and (ii) discrimination between malignant and non-neoplastic bone diseases, and compared their performance with human observers. Materials and MethodsAfter applying our exclusion criteria on 7188 patients from three different centers, 3772 and 2248 patients were enrolled for the first and second analyses, respectively. Data were split into two parts, including training and testing, while a fraction of training data were considered for validation. Ten different CNN models were applied to single- and dual-view input (posterior and anterior views) modes to find the optimal model for each analysis. In addition, three different methods, including squeeze-and-excitation (SE), spatial pyramid pooling (SPP), and attention-augmented (AA), were used to aggregate the features for dual-view input models. Model performance was reported through area under the receiver operating characteristic (ROC) curve (AUC), accuracy, sensitivity, and specificity and was compared with the DeLong test applied to ROC curves. The test dataset was evaluated by three nuclear medicine physicians (NMPs) with different levels of experience to compare the performance of AI and human observers. ResultsDenseNet121_AA (DensNet121, with dual-view input aggregated by AA) and InceptionResNetV2_SPP achieved the highest performance (AUC = 0.72) for the first and second analyses, respectively. Moreover, on average, in the first analysis, Inception V3 and InceptionResNetV2 CNN models and dual-view input with AA aggregating method had superior performance. In addition, in the second analysis, DenseNet121 and InceptionResNetV2 as CNN methods and dual-view input with AA aggregating method achieved the best results. Conversely, the performance of AI models was significantly higher than human observers for the first analysis, whereas their performance was comparable in the second analysis, although the AI model assessed the scans in a drastically lower time. ConclusionUsing the models designed in this study, a positive step can be taken toward improving and optimizing WBS interpretation. By training DL models with larger and more diverse cohorts, AI could potentially be used to assist physicians in the assessment of WBS images.

A population-based analysis of the presentation and outcomes of pediatric patients with osteosarcoma in Canada: a report from CYP-C.

Background:Frequently occurring in adolescents, osteosarcoma is the most common primary malignant bone disease, with a reported 15% of patients who present with metastasis. With advances in imaging and improvements in surgical care, an updated analysis is warranted on the outcomes of pediatric patients with osteosarcoma.Methods:We completed a retrospective review of pediatric patients who presented with osteosarcoma between 2001 and 2017, using The Cancer in Young People in Canada (CYP-C) national database. Data on 304 patients aged younger than 15 years were analyzed.Results:The proportion of patients who presented with metastasis was 23.0%. The overall 5-year survival (OS) for patients who presented with metastasis was 37.4%. Overall survival and event-free survival (EFS) were lower in these patients than in patients with localized disease (hazard ratio [HR] 4.3, p < 0.0001 and HR 3.1, p < 0.0001). For patients who presented with metastatic disease, the OS for those undergoing an operative intervention was 44.1% compared with 17.6% for those who did not undergo resection (p < 0.0001).Conclusion:The proportion of patients who presented with metastatic osteosarcoma in our population is higher than previously reported. Overall outcomes of patients with metastatic disease have not changed. Our data reaffirm a role for surgical resection in patients with metastasis with a need to explore new treatment strategies to improve the overall prognosis of these patients.

Trabecular metal augments in severe malignancy-associated acetabular bone loss.

Acetabular reconstruction is a challenging problem in orthopaedic oncology, especially in extended defects (Paprosky Type 3A and Type 3B). In revision total hip arthroplasty (THA), 1 option is trabecular metal (TM) augments with a porous metal acetabular component. This study evaluated the use of TM augments in periacetabular malignant bone disease. 15 patients were identified from our institutional database from 2000 to 2020 with either Paprosky Type 3A or Type 3B acetabular bone loss due to periacetabular malignancies that underwent at least 1 complex THA reconstruction with TM augments. Postoperative complications were documented, and clinical and radiographic outcomes were analysed. Radiological loosening or revision of the acetabular component were defined as endpoints. There were 7 primary and 8 metastatic cancer patients. 5 were Type 3A and 10 were Type 3B defects after tumour resection. The average follow-up time was 23.8 (range 1.5-47) months. 1 patient required revision for acetabular component loosening after 7 months from the initial implantation. An additional 4 patients required surgical intervention for infection, they had stable TM augments at latest follow-up. TM augments with a porous metal acetabular component may be an alternative to the traditional cemented constructs.

The impact of industrialization on malignant neoplastic disease of bone in England: A study of medieval and industrial samples

ObjectiveThe increasing prevalence of malignant disease has been associated with shifts in environmental, socioeconomic, and lifestyle risk factors as well as increased adult lifespan. We examine the relationship between malignant neoplasms affecting bone, age and industrialization. MaterialsPre-existing skeletal data from 11 medieval (1066–1547, n = 8973) and 14 industrial (1700–1890, n = 4748) cemeteries (N = 13,721) from England. MethodsContext number, sex, age-at-death, evidence of skeletal malignancy, and diagnosis were collated. The data were compared using chi square, Kolmogorov-Smirnov tests and logistic regression (α = 0.01). ResultsThere was a statistically significant increase in skeletal malignancy from 0.06 % in the medieval sample to 0.36 in the industrial sample (p < 0.001). Age had a strong relationship with malignancy (p = 0.003), sex did not (p = 0.464). Logistic regression revealed that time-period (p < 0.001) was a stronger predictor of skeletal malignancy than age-at-death (p = 0.002). ConclusionOur results confirm that even with the temporal increase in adult human lifespan the increase of malignant neoplasms of bone between the medieval and industrial time periods is still statistically significant. SignificanceThe augmented exposure to carcinogens and pollution during the Industrial Revolution had a strong effect on an individual’s susceptibility to developing malignant disease of bone. LimitationsThis meta-analysis relies upon previously gathered data and diagnosis from a large number of researchers and did not include radiographic or CT screening. Only malignant neoplasms that affected bone could be included. Suggestions for further researchIncreasing excavation and analysis of post-medieval cemeteries will provide more data. Multimethod approaches (radiography, CT, Micro-CT and histology) are encouraged.

A facile aqueous production of bisphosphonated-polyelectrolyte functionalized magnetite nanoparticles for pH-specific targeting of acidic-bone cells.

Bone malignancy treatment is being hindered due to the insufficient selectivity of therapeutic nanoparticles towards malignant bone sites. Polyelectrolyte functionalized magnetic nanoparticles having dually specific pH-sensing ability and bisphosphonate moieties, can be an effective solution for selective targeting of bone malignancies. First, polyelectrolyte was prepared via N-carboxycitraconyzation of chitosan (NCCS) followed by successive functionalization with alendronic acid (AL) and fluorescein isothiocyanate (FITC). Then, Fe3O4-NCCS-FITC-AL nanoparticles were synthesized by a facile one-step microwave-assisted aqueous method via in situ surface functionalization. The formation, crystal structure, and surface conjugation of Fe3O4 nanoparticles with polyelectrolytic stabilizer were confirmed by Fourier transform infrared spectroscopy, X-ray diffraction, and thermogravimetric analyses. Synthesized Fe3O4-NCCS-FITC-AL nanoparticles were superparamagnetic, colloidally stable and highly hemocompatible under physiological conditions. Moreover, at pH 5.0, Fe3O4-NCCS-FITC-AL nanoparticles formed a precipitate due to inversion of their surface charge. This pH-dependent charge-inversion drastically changed the interactions with erythrocytes and bones. Selective membranolysis of erythrocytes occurred at pH 5.0. The designed nanoparticles showed enough potential for selective targeting of pathological bone sites in early-stage magnetofluorescent imaging and as a therapeutics carrier to treat malignant bone diseases.

IVC filter placement in patients undergoing surgical treatment of bone or soft‐tissue tumors

Patients with cancer to bone or soft tissues undergoing orthopedic procedures may be unable to receive pharmacologic prophylaxis for venous thromboembolism (VTE). Inferior vena cava (IVC) filters may be an effective method to prevent fatal pulmonary embolism (PE) in these patients. Retrospective chart review performed for patients surgically treated for malignant disease of bone or soft tissue who had IVC filter placement. Type of surgery, anatomic region, and development of wound complications requiring repeat surgery were analyzed. From 2007 to 2018, 286 patients received IVC filters. Ten (3.5%) patients suffered deep vein thrombus (DVT) postoperatively. There was no acute fatal PE. Two patients suffered PE at 2 and 99 days postoperatively. Risk of DVT was comparable following surgery with endoprosthesis versus open reduction and internal fixation (p = 0.056) and with soft tissue versus bone involvement (p = 0.620). Three filter-related complications occurred. Patients disease at the femur had the highest rate of DVT. Following treatment of malignant disease of bone or soft-tissues, two patients with IVC filter placement experienced nonfatal PE and three patients experienced filter-related complications. No patients in this series experienced a fatal PE.

Image Fusion of Multislice Spiral CT with Magnetic Resonance Imaging (MRI) in the Diagnosis and Nursing of Malignant Bone Diseases Using ANOVA

This work aimed to analyze the diagnostic value of dynamic scanning of multislice spiral computed tomography (MSCT) and magnetic resonance imaging (MRI) for benign and malignant bone tumor and nursing intervention. 108 patients with bone tumor were selected as the research objects, all of which underwent MSCT and MRI scans. The accuracy, sensitivity, and specificity of MSCT, MRI, and MSCT + MRI for identifying benign and malignant bone tumors and nursing care were calculated, as well as the diagnostic accuracy of MSCT, MRI, and MSCT + MRI for different bone tumor pathological types. The results showed that the accuracy of MSCT + MRI (97.56%) in distinguishing benign and malignant bone lesions was remarkably higher relative to that of MSCT (85.91%) and MRI (89.85%) ( P &lt; 0.05 ). The sensitivity and specificity of MSCT + MRI (94.85%; 90.52%) in distinguishing benign and malignant bone lesions were obviously greater in contrast to those of MSCT (83.66%; 79.05%) and MRI (86.02%; 81.17%) ( P &lt; 0.05 ). The malignant misdiagnosis rate and malignant missing report rate of MSCT + MRI in distinguishing benign and malignant bone lesions were inferior to those of MSCT and MRI notably ( P &lt; 0.05 ). The accuracy of MSCT + MRI in distinguishing osteosarcoma, giant-cell tumor of bone (GCT), bone cyst, and osteofibrous dysplasia (OFD) was evidently higher versus that of MSCT and MRI ( P &lt; 0.05 ). The accuracy of MSCT + MRI in distinguishing osteofibroma and ganglioneuroma was greatly higher than that of MSCT and MRI ( P &lt; 0.05 ). The accuracy of MSCT + MRI in distinguishing osteofibroma and ganglioneuroma was 68.64% and 71.63%, respectively. In short, in contrast to the single MSCT and MRI examination, MSCT combined with MRI detection can effectively improve the accuracy of judgment for benign and malignant bone tumor lesions and nursing care and had higher sensitivity and specificity. MSCT combined with MRI had better performance in identifying osteosarcoma, GCT, bone cyst, and OFD but poor performance in osteofibroma and ganglioneuroma.

Baseline N-Telopeptide Levels Correlate with Risk of Skeletal Morbidity in Patients with Multiple Myeloma during Zoledronic Acid Therapy.

BACKGROUND: Biochemical markers of bone metabolism provide valuable information about rates of bone turnover in patients with malignant bone disease. N-telopeptide of type I collagen (NTX) is released during osteolysis and is indicative of pathologic increases in bone resorption. Elevated NTX levels recently have been correlated with increased risks of skeletal-related events (SREs, defined as pathologic fracture, surgery to bone, spinal cord compression, hypercalcemia of malignancy, and the requirement for palliative radiotherapy), disease progression, and death in patients with bone metastases from solid tumors (Coleman RE, et al. J Clin Oncol. 2005; 23:4925–4935; Brown J, et al. J Natl Cancer Inst . 2005; 97:59–69).METHODS: The current univariate analysis investigated the correlation between NTX levels at baseline and SREs (including palliative radiotherapy to bone) in patients with multiple myeloma who were treated with 4 mg zoledronic acid in a phase III clinical trial (Rosen LS, et al. Cancer J. 2001; 7:377–387).RESULTS: Forty-three patients had low NTX (< 50 nmol/mmol creatinine), 45 had moderate NTX (50 to < 100 nmol/mmol creatinine), and 18 had high NTX (≥ 100 nmol/mmol creatinine) at baseline. Patients with either moderate or high NTX at baseline had significantly increased risks of on-study SREs and significantly increased risks of experiencing their first SRE while on-study compared with patients with low NTX (Table). A similar correlation was also observed for pathologic fractures alone. The risk of first events was especially high in the high NTX group. There were no significant correlations between NTX levels and the requirement for palliative radiotherapy alone.Hazard Ratios for Time to Onset and Occurrence of On-Study SRE Compared With Low (< 50 nmol/mmol creatinine) NTX (P Value)SREPathologic fracturePalliative radiotherapyBaseline NTX levelOnset of first SREAny eventOnset of first eventAny eventOnset of first eventAny eventModerate*2.76 (.012)2.26 (.003)3.78 (.001)2.98 (< .001)1.21 (.777)1.61 (.386)High†6.80 (< .001)4.01 (.001)8.87 (< .001)5.35 (< .001)3.23 (.095)3.44 (.124)*50 to < 100 nmol/mmol creatinine.; † ≥ 100 nmol/mmol creatinine.Conclusions: Multiple myeloma patients with elevated baseline NTX levels have a significantly increased risk of experiencing SREs.

Whole-body MRI: a practical guide for imaging patients with malignant bone disease

Whole-body magnetic resonance imaging (MRI) is now a crucial tool for the assessment of the extent of systemic malignant bone disease and response to treatment, and forms part of national and international recommendations for imaging patients with myeloma or metastatic prostate cancer. Recent developments in scanners have enabled acquisition of good-quality whole-body MRI data within 45 minutes on modern MRI systems from all main manufacturers. This provides complimentary morphological and functional whole-body imaging; however, lack of prior experience and acquisition times required can act as a barrier to adoption in busy radiology departments. This article aims to tackle the former by reviewing the indications and providing guidance for technical delivery and clinical interpretation of whole-body MRI for patients with malignant bone disease.

Hypoxia-Inducible Factors Regulate Osteoclasts in Health and Disease.

Hypoxia-inducible factors (HIFs) have become key transcriptional regulators of metabolism, angiogenesis, erythropoiesis, proliferation, inflammation and metastases. HIFs are tightly regulated by the tissue microenvironment. Under the influence of the hypoxic milieu, HIF proteins allow the tissue to adapt its response. This is especially critical for bone, as it constitutes a highly hypoxic environment. As such, bone structure and turnover are strongly influenced by the modulation of oxygen availability and HIFs. Both, bone forming osteoblasts and bone resorbing osteoclasts are targeted by HIFs and modulators of oxygen tension. Experimental and clinical data have delineated the importance of HIF responses in different osteoclast-mediated pathologies. This review will focus on the influence of HIF expression on the regulation of osteoclasts in homeostasis as well as during inflammatory and malignant bone diseases.

A Stepwise Approach to Identify the Clinical Role of FDG PET-CT in Patients with Suspicious Bone Metastasis from an Unknown Primary Site

Objectives: In patients with suspicious bone metastasis, differential diagnosis and primary lesion identification is very important in optimizing treatment planning. The study was aimed to assign a step-wise approach based on image findings to identify the precise role of PET-CT in these patients.&#x0D; Patients and Methods: A total of 74 patients were enrolled with suspicious bone metastasis who underwent PET-CT for the evaluation of primary focus. Patients were classified into four groups with stepwise manners, firstly based on FDG positivity of bone lesions, then on multiplicity of positive bone uptake and finally on presence of extra-skeletal uptake. We analyzed the difference of distribution of follow-up results according to each group. In addition, we also investigated whether PET-CT had a role to guide biopsy sites.&#x0D; Results: Except for 7 patients without bone or extra-skeletal uptake, 44 patients were categorized in multiple bone and extra-skeletal uptake group (A), 12 in multiple bone uptake without extra-skeletal uptake group (B), 3 in single bone and extra-skeletal uptake group (C) and 8 in single bone uptake without extra-skeletal uptake group (D). In group A, 42/44 patients had metastatic bone disease; where primary lesion was correlating extra-skeletal uptake in 40 (91.0%) cases. Among the 12 patients of group B, 5 (41.7%) had primary malignant bone disease, 3 (25.0%) had benign bone lesions and 4 (33.3%) had metastatic bone disease but PET-CT failed to indicate the primary site. In group C, PET-CT positive extra-skeletal uptake sites were confirmed as primary lesions in all the 3 patients. Among the 8 patients of group D, 5 (62.5%) were benign bone disease, one (12.5%) was high grade sarcoma and the remaining two (25.0%) were metastatic bone disease where PET-CT failed to identify primary site. Additionally, there was significant (P = 0.0003) difference in prevalence of biopsy sites performed according to the presence of extra-skeletal uptake in PET-CT.&#x0D; Conclusion: Clinical impact of PET-CT was different according to groups classified with stepwise manners, which suggested that different strategies should be taken especially when there was not extra-skeletal uptake to optimize management plan. PET-CT also had a significant role in patients with extra-skeletal uptake lesion through guidance of easily approachable biopsy sites.&#x0D; Bangladesh J. Nuclear Med. 22(2): 95-102, Jul 2019

The Role of PINP in Diagnosis and Management of Metabolic Bone Disease.

Serum procollagen type I N-propeptide (PINP) is designated the reference marker of bone formation in osteoporosis; the reference marker for resorption is C-terminal telopeptide of type I collagen (CTX). PINP has very low circadian and biological variation, is not affected by food intake, and is very stable in serum after venepuncture. The two automated commercial assays for PINP provide similar results in subjects with normal renal function, allowing reference intervals to be used interchangeably. Bone turnover markers (BTM) are currently not recommended for fracture risk assessment and therefore not included in fracture risk calculators. In the management of osteoporosis, the main utility of BTM including PINP is for monitoring therapy, both antiresorptive as well as anabolic agents; monitoring is thought to help improve adherence. PINP as well as CTX may also be used in assessing offset of drug action following a pause in bisphosphonate therapy, to help decide when to re-instate therapy, or following cessation of denosumab therapy to assess efficacy of follow-on bisphosphonate therapy. PINP may also be used in the diagnosis of Paget's disease of bone as well as in monitoring response to therapy and for recurrence. Although BTM other than bone alkaline phosphatase are currently not recommended for use in metabolic bone disease of chronic kidney disease, PINP measured by assays specific to the intact molecule has potential in this condition. Further studies are needed to examine this area, as well as in malignant bone disease.