scholarly journals The Src Inhibitor AZD0530 Prevents the Development of Osteolytic Bone Disease in Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3018-3018
Author(s):  
Roy Heusschen ◽  
Joséphine Muller ◽  
Marilène Binsfeld ◽  
Erwan Plougonven ◽  
Nadia Mahli ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Osteoblast Differentiation ◽  
Osteoclast Differentiation ◽  
Disease Stage ◽  
Bone Lesions ◽  
Mrna Levels ◽  
Osteoblast Function ◽  
Src Inhibitor ◽  
Osteolytic Bone Disease

Abstract Destructive bone lesions due to osteolytic bone disease are a major cause of morbidity and mortality in multiple myeloma patients, occurring in more than 80% of cases. Underlying osteolytic bone disease is an uncoupling of the bone remodeling process, with an increased activity of osteoclasts and a decreased activity of osteoblasts. Current strategies to treat osteolytic bone disease focus on anti-resorptive agents, which do not rebuild bone loss. Src kinase has been implicated in both osteoclast and osteoblast function. In this study, we assessed the effect of Src inhibition with AZD0530 (saracatinib, Astra Zeneca) on the development of multiple myeloma and its associated osteolytic bone disease. We first determined Src family kinase expression in the multiple myeloma microenvironment and found that patient-derived myeloma cells express Src at low levels but disease stage does not correlate with Src expression levels. In accordance with the literature, Src mRNA expression was found to increase during osteoclast differentiation and decrease during osteoblast differentiation in publicly available microarray datasets. Next, we validated an inhibitory role of AZD0530 on osteoclast differentiation and function. At a pharmacological relevant concentration of 1 micromolar, AZD0530 inhibited the differentiation of RAW264.7 osteoclasts (Oc.N/FOV: 15.5+-1.6 treated vs. 53+-1.5 non-treated). AZD0530 treatment appeared to hamper efficient progenitor cell fusion and osteoclast polarization, reflected by a decrease of CTSK and DC-STAMP mRNA levels and a defective actin ring formation in treated cultures, which culminated in a complete inhibition of bone resorption. When assessing the effect of AZD0530 on osteoblast function we found that AZD0530 inhibits osteoblast differentiation, with a decreased expression of OSX and OCN, and alters osteoblast morphology. In vivo, AZD0530 did not alter myeloma cell bone marrow infiltration in both the 5TGM.1 (37+-6.3% AZD0530 treated vs. 25.2+-6.7% non-treated) and 5T2MM (26.1+-7.7% vs. 29.1+-6.4%) murine multiple myeloma models. However, bone health was significantly improved in both models following treatment with AZD0530. In the 5TGM.1 model multiple trabecular bone parameters were restored to levels observed in healthy control mice following AZD0530 treatment, including BV/TV (11.7+-0.3% treated vs. 6.4+-0.3% non-treated), Tb.N. (2.5+-6x10^-2/mm vs. 1.7+-9x10^-2/mm) and Tb.Th (46.2+-1micron vs. 37+-0.8micron). These results were confirmed in the 5T2MM model, which displays a more severe osteolytic bone disease. In addition, AZD0530 treatment resulted in an increase in cortical thickness (157.8+-0.8micron treated vs. 151.4+-0.7micron non-treated) and a decrease in the number and size of cortical lesions in 5TGM.1 mice. Finally, our findings were corroborated by histomorphometric analyses. In conclusion, we report a potent inhibitory effect of the Src inhibitor AZD0530 on the development of osteolytic bone disease in multiple myeloma. Our results indicate that AZD0530 exerts this effect via the modulation of both osteoclast and osteoblast function. These findings warrant further study of the feasibility and efficacy of AZD0530 to treat osteolytic bone disease in multiple myeloma patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals Circulating microRNAs Correlate with Multiple Myeloma and Skeletal Osteolytic Lesions

Cancers ◽  
2021 ◽  
Vol 13 (21) ◽  
pp. 5258
Author(s):  
Sara Reis Moura ◽  
Hugo Abreu ◽  
Carla Cunha ◽  
Cláudia Ribeiro-Machado ◽  
Carla Oliveira ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Area Under The Curve ◽  
Genetic Alterations ◽  
Disease Stage ◽  
Bone Lesions ◽  
Healthy Controls ◽  
Osteolytic Lesions ◽  
Circulating Micrornas ◽  
Myeloma Bone Disease

Multiple myeloma (MM) is the second most frequent hematological disease and can cause skeletal osteolytic lesions. This study aims to evaluate the expression of circulating microRNAs (miRNAs) in MM patients and to correlate those levels with clinicopathological features, including bone lesions. A panel of miRNAs associated with MM onset and progression, or with bone remodeling, was analyzed in the plasma of 82 subjects (47 MM patients; 35 healthy controls). Results show that miR-16-5p, miR-20a-5p, and miR-21-5p are differently expressed between MM patients and healthy controls. Receiver operating characteristic analyses indicate that their combined expression has potential as a molecular marker (Area Under the Curve, AUC of 0.8249). Furthermore, significant correlations were found between the analyzed miRNAs and disease stage, treatment, β2 microglobulin, serum albumin and creatinine levels, but not with calcium levels or genetic alterations. In this cohort, 65.96% of MM patients had bone lesions, the majority of which were in the vertebrae. Additionally, miR-29c-3p was decreased in patients with osteolytic lesions compared with patients without bone disease. Interestingly, circulating levels of miR-29b-3p correlated with cervical and thoracic vertebral lesions, while miR-195-5p correlated with thoracic lesions. Our findings suggest circulating miRNAs can be promising biomarkers for MM diagnosis and that their levels correlate with myeloma bone disease and osteolytic lesions.

scholarly journals Monoclonal immunoglobulins promote bone loss in multiple myeloma

Blood ◽  
2020 ◽  
Vol 136 (23) ◽  
pp. 2656-2666
Author(s):  
Marita Westhrin ◽  
Vlado Kovcic ◽  
Zejian Zhang ◽  
Siv H. Moen ◽  
Tonje Marie Vikene Nedal ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Sialic Acid ◽  
Bone Loss ◽  
Bone Disease ◽  
Osteoclast Differentiation ◽  
Osteolytic Bone Disease ◽  
Monoclonal Immunoglobulins ◽  
Diagnostic Criterion ◽  
Acid Precursor

Abstract Most patients with multiple myeloma develop a severe osteolytic bone disease. The myeloma cells secrete immunoglobulins, and the presence of monoclonal immunoglobulins in the patient’s sera is an important diagnostic criterion. Here, we show that immunoglobulins isolated from myeloma patients with bone disease promote osteoclast differentiation when added to human preosteoclasts in vitro, whereas immunoglobulins from patients without bone disease do not. This effect was primarily mediated by immune complexes or aggregates. The function and aggregation behavior of immunoglobulins are partly determined by differential glycosylation of the immunoglobulin-Fc part. Glycosylation analyses revealed that patients with bone disease had significantly less galactose on immunoglobulin G (IgG) compared with patients without bone disease and also less sialic acid on IgG compared with healthy persons. Importantly, we also observed a significant reduction of IgG sialylation in serum of patients upon onset of bone disease. In the 5TGM1 mouse myeloma model, we found decreased numbers of lesions and decreased CTX-1 levels, a marker for osteoclast activity, in mice treated with a sialic acid precursor, N-acetylmannosamine (ManNAc). ManNAc treatment increased IgG-Fc sialylation in the mice. Our data support that deglycosylated immunoglobulins promote bone loss in multiple myeloma and that altering IgG glycosylation may be a therapeutic strategy to reduce bone loss.

scholarly journals Blockade of Mer By the Small Molecule Inhibitor R992 Inhibits Multiple Myeloma and Its Associated Bone Disease By Restoring the Perturbed Bone Homeostasis

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 1922-1922 ◽  
Author(s):  
Janik Engelmann ◽  
Isabel Ben Batalla ◽  
Hanna Taipaleenmäki ◽  
Kristoffer Riecken ◽  
Victoria Gensch ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Osteoblast Differentiation ◽  
Biological Effects ◽  
Osteoclast Differentiation ◽  
Bone Homeostasis ◽  
Mineral Density ◽  
Trabecular Thickness ◽  
Dose Dependent

Abstract Despite many therapeutic advances in recent years Multiple Myeloma (MM) still remains incurable in the majority of the patients. In addition, MM patients suffer significantly from co-morbidities including bone pain and renal insufficiency. Therefore, the development of novel treatments is warranted. The TAMR family consists of Tyro3, Axl and Mer which represent evolving targets in cancer. We demonstrated that the role of TAMR is non-redundant in hematologic malignancies, with Axl exerting an important function in AML, but not in MM, where Mer represents a novel target. Therefore, we tested the therapeutic potential of the Mer-inhibitor R992, which has an 8-fold selectivity over Tyro3 and a 13-fold selectivity over Axl in preclinical MM models (Rigel, San Francisco, USA). R992 exerted a dose-dependent growth inhibition of U266, JJN3 and RPMI8226 cells in vitro (n=3, *p<0.001). Mechanistically, Mer blockade inhibited proliferation in 5-bromo-2′-deoxyuridine assays and induced apoptosis as shown by increased numbers of Annexin V+ cells (n=3,*p<0.05 and *p<0.001, respectively). To delineate signaling pathways mediating the biological effects of Mer blockade in MM cells we investigated key mediators of MM cell proliferation and survival. Here, we found reduced phosphorylation of Akt upon Mer inhibition with R992. Furthermore, R992 inhibited mitogen-activated protein kinase (MAPK) pathways Erk and p38. Subsequently, we investigated whether inhibition of Mer signaling increases chemosensitivity of MM cells. Combination treatment of R992 with bortezomib and cyclophosphamide demonstrated that Mer inhibition significantly increased sensitivity of MM cells to these established MM therapies. Oral administration of 60mg/kg R992 BID to mice significantly reduced tumor burden in the U266 systemic myeloma mouse model. The λ light chain concentration and the CD138+ MM cell load was reduced 2-fold in R992 treated mice compared to placebo-treated mice 8 weeks after injection (n=5/5, *p<0.05 and n=4/5, *p<0.05, respectively). Importantly, treatment with R992 resulted in a significant prolongation of overall survival by 15 days in the U266 model (median OS 73 vs. 88 days (n=13/12, *p<0.05). In addition, treatment with R992 prolonged survival in the more aggressive JJN3 model (median OS 24 vs. 27 days, n=9/7, *p<0.005). For further phenotyping of the effects of R992 we performed microcomputed tomography (µCT) and histological analysis of the tibias in the U266 model. µCT analysis of proximal tibia metaphyses revealed, that bone volume and bone mineral density (BMD) were significantly increased by R992 (n=7/7, *p<0.05). Moreover, analysis of the metaphyseal spongiosa showed that R992 could retard myeloma-mediated destruction of trabecular bone area measured by increased trabecular number and increased trabecular thickness (n=7/7, *p<0.05). Interestingly, R992 could also enlarge the metaphyseal diameter due to thickened cortical bone. Vice versa, overexpression of the Mer ligands Gas6 and Pros1 in U266 and JJN3 cells led to increased osteoclast and decreased osteoblast differentiation in vitro and more rapid and destructive myeloma bone disease in vivo. These data suggest that the expression of Mer ligands represent thus far unrecognized mediators of MM-induced perturbed bone homeostasis. To directly assess the effect of R992 on osteoclasts, we treated osteoclast cultures with R992 and observed an inhibition of osteoclast differentiation by R992 alone and in co-culture with myeloma cells. Western blot analysis confirmed, that Mer phosphorylation was reduced by R992, whereas the phosphorylation of Tyro3 was not altered. Concomitantly, phosphorylation of p38 and activation of non-canonical NFκB pathway showed a dose dependent reduction after Mer blockade. Interestingly, R992 led also to increased osteoblast differentiation and could restore myeloma mediated osteoblast inhibition in co-cultures of MM cells and osteoblasts. In summary, our data suggest that Mer blockade leads to inhibition of MM and its associated bone disease. Furthermore, the function of Mer in bone homeostasis promoting osteoclast and inhibiting osteoblast activity leads to the potential application of Mer inhibitors also in osteolytic bone metastases or osteoporosis. Disclosures Darwish: Rigel Pharmaceuticals: Employment. Bhamidipati:Rigel Pharmaceuticals: Employment. Masuda:Rigel Pharmaceuticals: Employment, Equity Ownership. Loges:BerGenBio: Consultancy, Membership on an entity's Board of Directors or advisory committees, Research Funding.

scholarly journals Glycosylationof Immunoglobulins Determine Bone Loss in Multiple Myeloma

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 4324-4324
Author(s):  
Marita Westhrin ◽  
Vlado Kovcic ◽  
Albert Bondt ◽  
Stephanie Holst ◽  
Zejian Zhang ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Loss ◽  
Bone Disease ◽  
Magnetic Beads ◽  
Conflicts Of Interest ◽  
Osteoclast Differentiation ◽  
Size Exclusion ◽  
Serum Samples ◽  
Osteolytic Bone Disease ◽  
Igg Glycosylation

About 80% of patients with multiple myeloma develop a severe osteolytic bone disease causing pain and fractures. The myeloma cells secrete immunoglobulins and the presence of monoclonal immunoglobulins in serum is a hallmark of the disease. Immunoglobulins play a role in bone loss, but have not been linked with the bone disease in multiple myeloma. In this work, we isolated immunoglobulins from serum of myeloma patients using protein G coupled magnetic beads and columns. We found that immunoglobulins from patients with bone disease (n=16) promoted osteoclast differentiation when added to human monocyte-derived pre-osteoclasts (p=0.006). We next fractionated the immunoglobulin samples by size-exclusion chromatography and found that the "osteoclast promoting activity" was in the high-molecular weight fractions, suggesting that they are in complexes. Since extent of complex formation may be determined by glycosylation, we examined whether there is a difference in immunoglobulin glycosylation between healthy controls and patients, and whether it changes during disease progression. To this end we analysed IgG glycosylation in serum samples from patients (n=72) and age and sex matched controls (n=51). These analyses showed that patient IgG was less galactosylated (p=0.02) and less sialylated (p=0.04) compared with control IgG. Moreover, patients with bone disease (n=43) had significantly less galactose on IgG compared with patients without bone disease (p=0.02, n=33). Supporting this data, we found that galactosidase treatment of immunoglobulins from patients without bone disease induced osteoclastogenesis (p=0.03), whereas addition of galactose to immunoglobulins of patients with bone disease removed their pro-osteoclastogenic effect (p=0.01). Further, the glycosyltransferases ST6GAL1 and B4GALT11, which add sialic acid and galactose to the sugar chain, respectively, are less expressed in plasma cells obtained from patients with bone disease (n=137) compared with those without (n=36, p<0.002, p<0.001, GSE755). Importantly, we observed a significant reduction of IgG glycosylation (p=0.02, n=8) in serum samples obtained from individual patients before and after the onset of bone disease. Taken together, our data support that immunoglobulins promote bone loss in multiple myeloma. Disclosures No relevant conflicts of interest to declare.

scholarly journals GDF15 Promotes Osteoclast Differentiation and High Serum GDF15 Levels Are Associated with Multiple Myeloma Bone Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 2065-2065
Author(s):  
Marita Westhrin ◽  
Siv Helen Moen ◽  
Toril Holien ◽  
Oddrun Elise Olsen ◽  
Anne Kærsgaard Mylin ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Disease ◽  
Osteoclast Differentiation ◽  
Serum Levels ◽  
High Serum ◽  
Healthy Controls ◽  
Serum Samples ◽  
Myeloma Bone Disease ◽  
Osteolytic Bone Disease

Abstract Introduction Growth differentiation factor 15 (GDF15) is a multifunctional growth factor of the transforming growth factor beta (TGFbeta) family that plays a complex role in several types of cancers. In multiple myeloma, GDF15 was recently shown to enhance the tumor-initiating and self-renewal potential of the cancer cells (Tanno et al, Blood 2014). Moreover, blood and bone marrow plasma levels of GDF15 are elevated in myeloma patients compared with healthy persons, and high serum levels are associated with a poor prognosis (Corre et al, Cancer Research 2012). GDF15 seems important for bone remodeling during hypoxia (Hino et al, JBMR 2012), and one study proposed GDF15 to increase osteoclast activation in prostate cancer metastasizing to bone (Wakchoure et al, Prostate 2009). Whether GDF15 plays a role in the bone disease of multiple myeloma is not well characterized. Aim Our aim was to investigate whether high GDF15 serum levels are associated with multiple myeloma bone disease and to characterize the effect of GDF15 on osteoclast differentiation in vitro. Methods GDF15 was measured in serum samples obtained at diagnosis from 138 myeloma patients and 58 age and sex-matched healthy controls. The patient serum samples were collected for the Nordic Myeloma Study Group during a randomized phase 3 clinical trial which compared the effect of two different doses of pamidronate on bone. The bone disease was therefore particularly well-characterized in this study (Gimsing et al, Lancet Oncol 2010). Peripheral blood mononuclear cells (PBMC) isolated from buffy coats were cultured in osteoclast medium (a-MEM with human serum (20%), M-CSF (30ng/ml) and RANKL (50ng/ml)) for up to 14 days with or without GDF15. Purchased pre-osteoclasts (Lonza Inc.) were cultured in purchased bullet kit (OC medium with M-CSF (33ng/ml) and RANKL (66ng/ml)) for 7 days with or without GDF15. Cells positive for tartrate resistant acidic phosphatase (TRAP) staining and with more than two nuclei were counted as osteoclasts. Results GDF15 was significantly higher in serum obtained from myeloma patients (median 1.08 ng/ml, range 27.91) compared with healthy controls (median 0.46 ng/ml, range 1.66, Independent samples Kruskal-Wallis test p< 0.0001). Moreover, serum GDF15 was elevated in patients with a more advanced osteolytic bone disease (n= 51, median 1.44 ng/ml, range 6.48) as compared to patients without osteolytic lesions (n= 16, median 0.84 ng/ml, range 10.62) at inclusion (p<0.05). The difference between serum GDF15 in patients with limited bone disease at inclusion (n=51, median 1.07 ng/ml, range 6.84) and patients with no bone disease at baseline was not significantly different. In vitro, addition of GDF15 (0-100 ng/ml) to osteoclast precursors or PBMC increased numbers of multi-nucleated TRAP positive cells in a dose dependent manner (n=3, O ng/ml GDF15 mean 25.7, SEM 5.9, 2 ng/ml GDF15 mean 29.7, SEM 4.3, 20 ng/ml GDF15 mean 38.7, SEM 4.9, 50 ng/ml GDF15 mean 53.3, SEM 11.6, 100 ng/ml GDF15 mean 78.7 SEM 7.8). OPG inhibited the pro-osteoclastogenic activity of GDF15 inferring that the effect is mediated by RANKL. Hence, GDF15 increases osteoclast differentiation. Conclusion Serum GDF15 is elevated in myeloma patients with advanced osteolytic bone disease compared to patients with no lesions. GDF15 increases osteoclast differentiation in vitro. Hence, GDF15 could play a role in regulating bone remodeling in myeloma patients. Disclosures No relevant conflicts of interest to declare.

Bone disease as the first manifestation of systemic AL-amyloidosis

2020 ◽  
Vol 92 (7) ◽  
pp. 85-89
Author(s):  
L. P. Mendeleeva ◽  
I. G. Rekhtina ◽  
A. M. Kovrigina ◽  
I. E. Kostina ◽  
V. A. Khyshova ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Bone Disease ◽  
Plasma Cells ◽  
Interventricular Septum ◽  
Bone Destruction ◽  
Amyloid Deposition ◽  
Bone Lesions ◽  
Al Amyloidosis ◽  
Linear Type

Our case demonstrates severe bone disease in primary AL-amyloidosis without concomitant multiple myeloma. A 30-year-old man had spontaneous vertebral fracture Th8. A computed tomography scan suggested multiple foci of lesions in all the bones. In bone marrow and resected rib werent detected any tumor cells. After 15 years from the beginning of the disease, nephrotic syndrome developed. Based on the kidney biopsy, AL-amyloidosis was confirmed. Amyloid was also detected in the bowel and bone marrow. On the indirect signs (thickening of the interventricular septum 16 mm and increased NT-proBNP 2200 pg/ml), a cardial involvement was confirmed. In the bone marrow (from three sites) was found 2.85% clonal plasma cells with immunophenotype СD138+, СD38dim, СD19-, СD117+, СD81-, СD27-, СD56-. FISH method revealed polysomy 5,9,15 in 3% of the nuclei. Serum free light chain Kappa 575 mg/l (/44.9) was detected. Multiple foci of destruction with increased metabolic activity (SUVmax 3.6) were visualized on PET-CT, and an surgical intervention biopsy was performed from two foci. The number of plasma cells from the destruction foci was 2.5%, and massive amyloid deposition was detected. On CT scan foci of lesions differed from bone lesions at multiple myeloma. Bone fragments of point and linear type (button sequestration) were visualized in most of the destruction foci. The content of the lesion was low density. There was no extraossal spread from large zones of destruction. There was also spontaneous scarring of the some lesions (without therapy). Thus, the diagnosis of multiple myeloma was excluded on the basis based on x-ray signs, of the duration of osteodestructive syndrome (15 years), the absence of plasma infiltration in the bone marrow, including from foci of bone destruction by open biopsy. This observation proves the possibility of damage to the skeleton due to amyloid deposition and justifies the need to include AL-amyloidosis in the spectrum of differential diagnosis of diseases that occur with osteodestructive syndrome.

scholarly journals A Molecular Signature of Circulating MicroRNA Can Predict Osteolytic Bone Disease in Multiple Myeloma

Cancers ◽  
2021 ◽  
Vol 13 (15) ◽  
pp. 3877
Author(s):  
Aristea-Maria Papanota ◽  
Panagiotis Tsiakanikas ◽  
Christos K. Kontos ◽  
Panagiotis Malandrakis ◽  
Christine-Ivy Liacos ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Logistic Regression ◽  
Bone Disease ◽  
Characteristic Curve ◽  
Molecular Signature ◽  
Circulating Microrna ◽  
Prognostic Role ◽  
Clinical Value ◽  
Osteolytic Bone Disease ◽  
Circulating Levels

Background: Multiple myeloma bone disease (MMBD) constitutes a common and severe complication of multiple myeloma (MM), impacting the quality of life and survival. We evaluated the clinical value of a panel of 19 miRNAs associated with osteoporosis in MMBD. Methods: miRNAs were isolated from the plasma of 62 newly diagnosed MM patients with or without MMBD. First-strand cDNA was synthesized, and relative quantification was performed using qPCR. Lastly, we carried out extensive biostatistical analysis. Results: Circulating levels of let-7b-5p, miR-143-3p, miR-17-5p, miR-214-3p, and miR-335-5p were significantly higher in the blood plasma of MM patients with MMBD compared to those without. Receiver operating characteristic curve and logistic regression analyses showed that these miRNAs could accurately predict MMBD. Furthermore, a standalone multi-miRNA–based logistic regression model exhibited the best predictive potential regarding MMBD. Two of those miRNAs also have a prognostic role in MM since survival analysis indicated that lower circulating levels of both let-7b-5p and miR-335-5p were associated with significantly worse progression-free survival, independently of the established prognostic factors. Conclusions: Our study proposes a miRNA signature to facilitate MMBD diagnosis, especially in ambiguous cases. Moreover, we provide evidence of the prognostic role of let-7b-5p and miR-335-5p as non-invasive prognostic biomarkers in MM.

scholarly journals Comparison of the diagnostic performance and impact on management of 18F-FDG PET/CT and whole-body MRI in multiple myeloma

2021 ◽  
Author(s):  
Olwen Westerland ◽  
◽  
Ashik Amlani ◽  
Christian Kelly-Morland ◽  
Michal Fraczek ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Clinical Data ◽  
Bone Disease ◽  
Fdg Pet ◽  
Diagnostic Performance ◽  
Whole Body ◽  
Bone Lesions ◽  
Pet Ct ◽  
18F Fdg ◽  
Fdg Pet Ct

Abstract Purpose Comparative data on the impact of imaging on management is lacking for multiple myeloma. This study compared the diagnostic performance and impact on management of 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT) and whole-body magnetic resonance imaging (WBMRI) in treatment-naive myeloma. Methods Forty-six patients undergoing 18F-FDG PET/CT and WBMRI were reviewed by a nuclear medicine physician and radiologist, respectively, for the presence of myeloma bone disease. Blinded clinical and imaging data were reviewed by two haematologists in consensus and management recorded following clinical data ± 18F-FDG PET/CT or WBMRI. Bone disease was defined using International Myeloma Working Group (IMWG) criteria and a clinical reference standard. Per-patient sensitivity for lesion detection was established. McNemar test compared management based on clinical assessment ± 18F-FDG PET/CT or WBMRI. Results Sensitivity for bone lesions was 69.6% (32/46) for 18F-FDG PET/CT (54.3% (25/46) for PET component alone) and 91.3% (42/46) for WBMRI. 27/46 (58.7%) of cases were concordant. In 19/46 patients (41.3%) WBMRI detected more focal bone lesions than 18F-FDG PET/CT. Based on clinical data alone, 32/46 (69.6%) patients would have been treated. Addition of 18F-FDG PET/CT to clinical data increased this to 40/46 (87.0%) patients (p = 0.02); and WBMRI to clinical data to 43/46 (93.5%) patients (p = 0.002). The difference in treatment decisions was not statistically significant between 18F-FDG PET/CT and WBMRI (p = 0.08). Conclusion Compared to 18F-FDG PET/CT, WBMRI had a higher per patient sensitivity for bone disease. However, treatment decisions were not statistically different and either modality would be appropriate in initial staging, depending on local availability and expertise.

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