Newly Diagnosed Multiple Myeloma Patients with Skeletal-Related Events and Abnormal MRI Pattern Have Poor Survival Outcomes: A Prospective Study on 370 Patients.

Contemporary information is sparse on the frequency of skeletal-related events (SREs) in multiple myeloma (MM) patients at a population-based level in the era of novel agents. In this context, we conducted this single-center, prospective, observational study to determine the incidence of SREs among newly diagnosed MMs (NDMM) and to explore the possible correlations with disease characteristics, imaging finding, and patient prognosis. A total of 370 patients with available baseline MRIs were included. Among them, 208 (56%) presented with at least one SRE at diagnosis. Fractures were the most common reported SREs (48%). The incidence of SREs at diagnosis was higher in patients with osteolytic lesions, abnormal MRI pattern, hypercalcemia, and at least 60% bone marrow infiltration by plasma cells. Importantly, the patients with normal MRI pattern, who did not present with SREs at diagnosis, had statistically significant improved median OS in comparison with the patients who had abnormal MRI patterns and/or the presence of SREs at diagnosis (9.3 vs. 6.6 years, p = 0.048). Our data, which represent one of a few systematic reports on the incidence and characteristics of SREs in the era of novel agents, was indicative of a high incidence of SREs at the time of MM diagnosis. Early detection of myeloma bone disease and tailored patient management are essential to optimize patient outcomes.

Comparison of MRI Features of Fat Fraction and ADC for Early Treatment Response Assessment in Participants with Multiple Myeloma.

Background An imaging-based predictor of response could provide prognostic information early during treatment course in patients with multiple myeloma (MM). Purpose To investigate if very early changes in bone marrow relative fat fraction (rFF) and apparent diffusion coefficient (ADC) histogram metrics, occurring after one cycle of induction therapy in participants with newly diagnosed MM, could help predict overall best response status. Materials and Methods This prospective study included participants with MM who were enrolled between August 2014 and December 2017. Histogram metrics were extracted from ADC and rFF maps from MRI examinations performed before treatment and after the first treatment cycle. Participants were categorized into the very good partial response (VGPR) or better group and the less than VGPR group per the International Myeloma Working Group response criteria. ADC and rFF map metrics for predicting treatment response were compared using the Wilcoxon rank test, and the false discovery rate (FDR) was used to correct for multiple comparisons. Results A total of 23 participants (mean age, 65 years ± 11 [SD]; 13 men) were evaluated. There was no evidence of a difference in ADC metrics between the two responder groups after correcting for multiple comparisons. The rFF histogram changes between pretreatment MRI and MRI after the first treatment cycle (ΔrFF) that provided significant differences between the VGPR or better and less than VGPR groups were as follows: ΔrFF_10th Percentile (median, 0.5 [95% CI: 0, 1] vs -2.5 [95% CI: -5.1, 0.1], respectively), ΔrFF_90th Percentile (median, 2 [95% CI: 1, 6.8] vs -0.5 [95% CI: -1, 0]), ΔrFF_Mean (median, 3.4 [95% CI: 0.3, 7.6] vs -1.1 [95% CI: -1.8, -0.7]), and ΔrFF_Root Mean Squared (median, 3.2 [95% CI: 0.3, 6.1] vs -0.7 [95% CI: -1.3, -0.4]) (FDR-adjusted P = .03 for all), and the latter two also presented mean group increases in the VGPR or better group that were above the upper 95% CI limit for repeatability. Conclusion Very early changes in bone marrow relative fat fraction histogram metrics, calculated from MRI examination at baseline and after only one cycle of induction therapy, may help to predict very good partial response or better in participants with newly diagnosed multiple myeloma. © RSNA, 2022 Online supplemental material is available for this article.

Whole-Body Low-Dose CT in Multiple Myeloma: Diagnostic Value of Appendicular Medullary Patterns of Attenuation.

OBJECTIVE. The purpose of this article is to analyze whole-body low-dose CT-detected appendicular medullary patterns of attenuation in patients with newly diagnosed multiple myeloma and to determine the diagnostic performance of whole-body low-dose CT in detecting diffuse marrow infiltration. MATERIALS AND METHODS. A total of 76 patients with myeloma who underwent whole-body low-dose CT and spinal MRI at initial assessment were retrospectively analyzed. The medullary cavities of femurs and humeri were evaluated qualitatively and quantitatively on CT. Medullary attenuation and SD-to-mean attenuation ratio were recorded for each long bone. The pattern of marrow involvement on spinal MRI was used as reference. The chi-square test was used to evaluate the relationship between the CT-based appendicular medullary cavity pattern and the MRI pattern, and ROC analysis was performed to assess the diagnostic accuracy of CT attenuation measurements for the differentiation between diffuse and mixed CT-based appendicular medullary cavity patterns. RESULTS. Medullary attenuation differed significantly among mixed, nodular, and diffuse CT-based appendicular medullary cavity patterns in the femurs (mean, 34.23 HU and range, 15-61 HU; mean, 66.26 HU and range, 26-104 HU; mean, 92.80 HU and range, 53-127 HU, respectively) and humeri (mean, 22.18 HU and range, 9-41; mean, 61.18 HU and range, 23-93 HU; mean, 77.50 and range, 25-105 HU, respectively). To discriminate between diffuse and mixed CT-based appendicular medullary cavity patterns, optimal cutoff attenuation values were 63 HU (sensitivity, 97.7%; specificity, 100.0%) for the femurs, and 52 HU (sensitivity, 97.4%; specificity, 100.0%) for the humeri. A total of 24 of 30 (80.0%) patients with a diffuse MRI pattern showed a diffuse CT-based appendicular medullary cavity pattern on whole-body low-dose CT, and all patients with a diffuse CT-based appendicular medullary cavity pattern also showed a diffuse pattern on MRI. CONCLUSION. According to analysis of peripheral medullary patterns of attenuation, whole-body low-dose CT can identify patients with multiple myeloma with diffuse marrow involvement.

Cardiac Magnetic Resonance Versus Single-Photon Emission Computed Tomography for Detecting Coronary Artery Disease and Myocardial Ischemia: Comparison with Coronary Angiography.

BACKGROUND: This study aimed to compare the diagnostic accuracy of stress single-photon emission computed tomography (SPECT) and stress cardiac magnetic resonance (CMR) for the assessment of coronary artery disease (CAD) in the same patients, using coronary angiography as the reference standard. METHODS: Thirty patients with known or suspected CAD who were referred for exercise SPECT myocardial perfusion imaging (MPI) for the evaluation of myocardial ischemia underwent stress CMR MPI and computed tomography coronary angiography (CTCA) or selective coronary angiography (SCA). The data from the two stress modalities were compared against the data from angiography. RESULTS: In our study population, 30% of the recruited subjects had significant CAD. The CMR sensitivity for the detection of significant CAD and/or myocardial ischemia was 89% and specificity was 76%. For SPECT, the corresponding sensitivity was 78% and specificity was 52%. The negative predictive value was 92% for CMR and 83% for SPECT. The receiver-operating characteristic (ROC) analysis evaluating the presence of significant CAD, CMR (area under the curve (AUC) 0.78) outperformed SPECT (AUC 0.59) (p < 0.01). The ROC analysis evaluating the presence of myocardial ischemia was also in favor of CMR (AUC 0.82) versus SPECT (AUC 0.67) (p < 0.01). CONCLUSIONS: CMR has high diagnostic accuracy for the detection of CAD and stress-induced ischemia and appears to outperform SPECT. CMR may thus be the preferred noninvasive imaging modality to assess patients with known or suspected CAD.

Apidima Cave fossils provide earliest evidence of Homo sapiens in Eurasia.

Two fossilized human crania (Apidima 1 and Apidima 2) from Apidima Cave, southern Greece, were discovered in the late 1970s but have remained enigmatic owing to their incomplete nature, taphonomic distortion and lack of archaeological context and chronology. Here we virtually reconstruct both crania, provide detailed comparative descriptions and analyses, and date them using U-series radiometric methods. Apidima 2 dates to more than 170 thousand years ago and has a Neanderthal-like morphological pattern. By contrast, Apidima 1 dates to more than 210 thousand years ago and presents a mixture of modern human and primitive features. These results suggest that two late Middle Pleistocene human groups were present at this site-an early Homo sapiens population, followed by a Neanderthal population. Our findings support multiple dispersals of early modern humans out of Africa, and highlight the complex demographic processes that characterized Pleistocene human evolution and modern human presence in southeast Europe.

Guidelines for Acquisition, Interpretation, and Reporting of Whole-Body MRI in Myeloma: Myeloma Response Assessment and Diagnosis System (MY-RADS).

Acknowledging the increasingly important role of whole-body MRI for directing patient care in myeloma, a multidisciplinary, international, and expert panel of radiologists, medical physicists, and hematologists with specific expertise in whole-body MRI in myeloma convened to discuss the technical performance standards, merits, and limitations of currently available imaging methods. Following guidance from the International Myeloma Working Group and the National Institute for Clinical Excellence in the United Kingdom, the Myeloma Response Assessment and Diagnosis System (or MY-RADS) imaging recommendations are designed to promote standardization and diminish variations in the acquisition, interpretation, and reporting of whole-body MRI in myeloma and allow response assessment. This consensus proposes a core clinical protocol for whole-body MRI and an extended protocol for advanced assessments. Published under a CC BY 4.0 license. Online supplemental material is available for this article.

Recommendations for acquisition, interpretation and reporting of whole body low dose CT in patients with multiple myeloma and other plasma cell disorders: a report of the IMWG Bone Working Group.

Whole Body Low Dose CT (WBLDCT) has important advantages as a first-line imaging modality for bone disease assessment in patients with plasma cell disorders and has been included in the 2014 International Myeloma Working Group (IMWG) criteria for multiple myeloma (MM) definition. Nevertheless, standardization guidelines for the optimal use of WBLDCT in MM patients are still lacking, preventing its more widespread use, both in daily practice and clinical trials. The aim of this report by the Bone Group of the IMWG is to provide practical recommendations for the acquisition, interpretation and reporting of WBLDCT in patients with multiple myeloma and other plasma cell disorders.

A Novel Metal-Based Imaging Probe for Targeted Dual-Modality SPECT/MR Imaging of Angiogenesis.

Superparamagnetic iron oxide nanoparticles with well-integrated multimodality imaging properties have generated increasing research interest in the past decade, especially when it comes to the targeted imaging of tumors. Bevacizumab (BCZM) on the other hand is a well-known and widely applied monoclonal antibody recognizing VEGF-A, which is overexpressed in angiogenesis. The aim of this proof-of-concept study was to develop a dual-modality nanoplatform for in vivo targeted single photon computed emission tomography (SPECT) and magnetic resonance imaging (MRI) of tumor vascularization. Iron oxide nanoparticles (IONPs) have been coated with dimercaptosuccinic acid (DMSA), for consequent functionalization with the monoclonal antibody BCZM radiolabeled with 99mTc, via well-developed surface engineering. The IONPs were characterized based on their size distribution, hydrodynamic diameter and magnetic properties. In vitro cytotoxicity studies showed that our nanoconstruct does not cause toxic effects in normal and cancer cells. Fe3O4-DMSA-SMCC-BCZM-99mTc were successfully prepared at high radiochemical purity (>92%) and their stability in human serum and in PBS were demonstrated. In vitro cell binding studies showed the ability of the Fe3O4-DMSA-SMCC-BCZM-99mTc to bind to the VEGF-165 isoform overexpressed on M-165 tumor cells. The ex vivo biodistribution studies in M165 tumor-bearing SCID mice showed high uptake in liver, spleen, kidney and lungs. The Fe3O4-DMSA-SMCC-BCZM-99mTc demonstrated quick tumor accumulation starting at 8.9 ± 1.88%ID/g at 2 h p.i., slightly increasing at 4 h p.i. (16.21 ± 2.56%ID/g) and then decreasing at 24 h p.i. (6.01 ± 1.69%ID/g). The tumor-to-blood ratio reached a maximum at 24 h p.i. (~7), which is also the case for the tumor-to-muscle ratio (~18). Initial pilot imaging studies on an experimental gamma-camera and a clinical MR camera prove our hypothesis and demonstrate the potential of Fe3O4-DMSA-SMCC-BCZM-99mTc for targeted dual-modality imaging. Our findings indicate that Fe3O4-DMSA-SMCC-BCZM-99mTc IONPs could serve as an important diagnostic tool for biomedical imaging as well as a promising candidate for future theranostic applications in cancer.

Functional and molecular MRI of the bone marrow in multiple myeloma.

MRI plays an important role in the management of patients with plasma cell neoplasms and has been recognized as a biomarker of malignancy in the novel criteria for the diagnosis of multiple myeloma. Functional and molecular MRI techniques such as diffusion-weighted imaging (spinal or whole body), intravoxel incoherent motion, and dynamic contrast enhanced MRI, provide additional information related to tumor cellularity and angiogenesis, which may have prognostic implications for patients with smoldering and symptomatic myeloma. These non-invasive functional techniques are also being evaluated as imaging biomarkers for response assessment in myeloma patients. The purpose of this article is to provide a comprehensive critical review on the current use and potential future applications of these advanced MRI techniques in multiple myeloma. In addition, we will address the technologies involved and describe the qualitative and quantitative characteristics of normal bone marrow with these techniques.

Pre- and postoperative magnetic resonance imaging (MRI) findings in patients treated with laparoscopic sacrocolpopexy. Is it a safe procedure for all patients?

INTRODUCTION: Laparoscopic sacrocolpopexy (LSCP) is a reference operation for apical compartment prolapse repair. Aim of this study is to describe the early and midterm postoperative MRI findings of the lumbosacral region (LSR) in patients undergoing LSCP and to detect any imaging changes that the presence of the mesh may cause on patients with preexisting degenerative disease of the LSR. METHODS: Patients with POP-Q grade III and IV uterovaginal or vaginal vault prolapse who were considered eligible for LSCP were invited to participate. An MRI of the LSR was performed preoperatively and then 3 and 12 months postoperatively. Patients with vaginal vault prolapse underwent LSCP, while women with uterovaginal prolapse were treated with the vaginally assisted laparoscopic sacrocolpopexy (VALS). RESULTS: A total of 30 patients were included in the study; 18 (60%) underwent LSCP and 12 (40%) VALS. On preoperative MRIs, 83.3% (25/30) of patients had degenerative changes and 70% (21/30) reported having low back pain (LBP). Postoperative MRIs did not reveal any imaging changes compared to the preoperative MRI findings both for patients with or without preexisting degenerative abnormalities of the LSR. No significant changes in the LBP score were observed postoperatively. CONCLUSIONS: Any bone marrow or soft-tissue changes at MRIs of the LSR early after the insertion of a synthetic mesh, does not constitute an expected postoperative finding and should raise the suspicion of an ongoing inflammatory or infectious spinal process (spondylodiscitis). Additionally, LSCP seems to be a safe surgical approach for women with preexisting degenerative disease of the LSR.

Dynamic contrast-enhanced magnetic resonance imaging parameters correlate with advanced revised-ISS and angiopoietin-1/angiopoietin-2 ratio in patients with multiple myeloma.

The aim of the study was to assess the value of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) in patients with newly diagnosed multiple myeloma (MM) who were treated with novel anti-myeloma agents. We studied 60 previously untreated MM patients at diagnosis, 14 with smoldering MM (SMM) and 5 with MGUS. All patients underwent MRI of the thoracolumbar spine and pelvis before the administration of any kind of therapy, and DCE-MRI was performed. The MRI perfusion parameters evaluated were wash-in (WIN), washout (WOUT), time-to-peak (TTPK), time-to-maximum slope (TMSP), and the WIN/TMSP ratio. The following serum levels of angiogenic cytokines were measured on the day of MRI: VEGF, angiogenin (Ang), angiopoietin-1 (Angp-1), and -2 (Angp-2). Symptomatic MM patients had increased WIN compared to SMM (p < 0.05) and MGUS patients (p = 0.001). TTPK was decreased, and WIN/TMSP was increased in both symptomatic and SMM patients compared to MGUS patients (p < 0.05). Symptomatic MM patients had decreased TMSP compared to MGUS patients. The Angp-1/Angp-2 ratio was reduced in symptomatic MM compared to SMM (p = 0.017) and MGUS patients (p < 0.001). TTPK correlated with Angp-1/Angp-2 ratio and importantly with R-ISS. Patients with R-ISS-3 had lower TTPK median value (23 s, range 18-29 s) compared to patients with R-ISS-2 (48 s, range 27-68 s) and patients with R-ISS-1 MM (54 s, range 42-76 s; p ANOVA = 0.01). A subset of patients with low TTPK (lower quartile) had shorter time to progression compared to all other patients. These data suggest that certain DCE-MRI parameters correlate with R-ISS and adverse prognostic features of angiogenesis, such as the ratio of Angp-1/Angp-2.

Quantitative Diffusion-weighted Imaging of the Bone Marrow: An Adjunct Tool for the Diagnosis of a Diffuse MR Imaging Pattern in Patients with Multiple Myeloma.

Purpose To evaluate the apparent diffusion coefficients (ADCs) of magnetic resonance (MR) imaging patterns in the bone marrow of patients with multiple myeloma (MM) and to determine a threshold ADC that may help distinguish a diffuse from a normal pattern with high accuracy. Materials and Methods This prospective study was approved by the ethics review board, and informed consent was obtained. Ninety-nine patients with newly diagnosed, untreated MM and 16 healthy control subjects underwent spinal MR imaging including diffusion-weighted imaging, and bone marrow ADCs were calculated. Pattern assignment was based on visual assessment of conventional MR images. The Kruskal-Wallis H test, the Mann-Whitney test, and the one-way analysis of variance were used to compare ADCs between patient subsets and control subjects, and a receiver operating characteristic analysis was performed. Results Mean ADCs ± standard deviation in patients with MM for the normal, focal, and diffuse MR imaging patterns were 0.360 × 10-3 mm2/sec ± 0.110, 1.046 × 10-3 mm2/sec ± 0.232, and 0.770 × 10-3 mm2/sec ± 0.135, respectively. There were significant differences in ADCs between diffuse and normal (P < .001), diffuse and focal (P < .001), and focal and normal (P < .001) patterns. Patients with a diffuse pattern had more features of advanced disease, higher international staging system score, increased incidence of high-risk cytogenetics, and higher revised international staging system score. ADCs greater than 0.548 × 10-3 mm2/sec showed 100% sensitivity (26 of 26) and 98% specificity (48 of 49) for the diagnosis of a diffuse (vs normal) MR imaging pattern, whereas an ADC greater than 0.597 × 10-3 mm2/sec showed 96% sensitivity (25 of 26) and 100% specificity (49 of 49). Conclusion ADCs of MR imaging patterns in patients with MM differ significantly. A diffuse MR imaging pattern can be distinguished more objectively from a normal MR imaging pattern by adding quantitative diffusion-weighted imaging to standard MR imaging protocols. © RSNA, 2016 Online supplemental material is available for this article.

The Role of Imaging in the Treatment of Patients With Multiple Myeloma in 2016.

The novel criteria for the diagnosis of symptomatic multiple myeloma have revealed the value of modern imaging for the management of patients with myeloma. Whole-body low-dose CT (LDCT) has increased sensitivity over conventional radiography for the detection of osteolytic lesions, and several myeloma organizations and institutions have suggested that whole-body LDCT should replace conventional radiography for the work-up of patients with myeloma. MRI is the best imaging method for the depiction of marrow infiltration by myeloma cells. Whole-body MRI (or at least MRI of the spine and pelvis if whole-body MRI is not available) should be performed for all patients with smoldering multiple myeloma with no lytic lesions to look for occult disease, which may justify treatment. In addition, MRI accurately illustrates the presence of plasmacytomas, spinal cord, and/or nerve compression for surgical intervention or radiation therapy; it is also recommended for the work-up of solitary bone plasmacytoma, and it may distinguish malignant from benign fractures (which is very important in cases of patients in biochemical remission with no other signs of progression). Diffusion weighted imaging (DWI) seems to improve MRI diagnosis in patients with myeloma. PET/CT is a functional imaging technique, more sensitive than conventional radiography for the detection of lytic lesions, which probably allows better definition of complete response and minimal residual disease compared with all other imaging methods. PET/CT has shown the best results in the follow-up of patients with myeloma and has an independent prognostic value both at diagnosis and following treatment. PET/CT can also be used for the work-up of solitary bone plasmacytoma and nonsecretory myeloma.

Ultrasmall particles for Gd-MRI and (68) Ga-PET dual imaging.

Nanoparticles made of a polysiloxane matrix and surrounded by 1,4,7,10-tetraazacyclododecane-1-glutaric anhydride-4,7,10-triacetic acid (DOTAGA)[Gd(3+) ] and 2,2'-(7-(1-carboxy-4-((2,5-dioxopyrrolidin-1-yl)oxy)-4-oxobutyl)-1,4,7-triazonane-1,4-diyl)diacetic acid) NODAGA[(68) Ga(3+) ] have been synthesized for positron emission tomography/magnetic resonance (PET/MRI) dual imaging. Characterizations were carried out in order to determine the nature of the ligands available for radiolabelling and to quantify them. High radiolabelling purity (>95%) after (68) Ga labelling was obtained. The MR and PET images demonstrate the possibility of using the nanoparticles for a combined PET/MR imaging scanner. The images show fast renal elimination of the nanoparticles after intravenous injection.

Sclerostin: a possible target for the management of cancer-induced bone disease.

INTRODUCTION: Sclerostin is a cysteine-knot-containing protein, which is produced by osteocytes and inhibits osteoblast function. The aim of this review is to summarize the data about the role of sclerostin in cancer-induced bone disease. AREAS COVERED: We performed a thorough search for articles in the PubMed using the words "sclerostin, cancer, multiple myeloma", and for similar abstracts that were presented in the ASH and ASCO annual meetings (2005 - 2011). In multiple myeloma, sclerostin is produced by myeloma cells and elevated in the serum or the plasma of the patients, and correlates with extensive bone disease and adverse myeloma features. In prostate cancer, sclerostin expression is reduced and in combination with bone morhogenetic protein-6 and noggin expression may serve as prognostic predictor for metastatic progression. In breast cancer, in vitro data suggest that the malignant cell induces the expression of sclerostin to inhibit osteoblasts in the metastatic bone area. EXPERT OPINION: Sclerostin may play a role in inhibiting bone formation in the biology of bone metastases in breast cancer and of myeloma-related bone disease. The results of phase I/II studies with anti-sclerostin drugs in subjects with low bone mass may lead to the potential clinical investigation of these agents in cancer-induced bone disease.

Diffuse pattern of bone marrow involvement on magnetic resonance imaging is associated with high risk cytogenetics and poor outcome in newly diagnosed, symptomatic patients with multiple myeloma: a single center experience on 228 patients.

Magnetic Resonance Imaging (MRI) and specific cytogenetic abnormalities offer important prognostic information for myeloma patients. However, limited data are available about the association between cytogenetic abnormalities and MRI patterns of marrow infiltration. To address this issue, we analyzed 228 consecutive newly diagnosed, symptomatic patients who were diagnosed and treated in a single center. On bone marrow MR images, 95 (41%) patients had diffuse, 94 (41%) had focal, 35 (15%) were normal, and 4 (1.7%) patients had variegated pattern of marrow infiltration. High risk cytogenetics were more commonly observed with diffuse MRI pattern (50% vs. 31% in focal and normal patterns). Patients with diffuse MRI pattern had poorer survival compared to others and responded better to novel agent-based therapies than to conventional chemotherapy (objective response: 88% vs. 46%, P < 0.001). There was a significant improvement of patients' survival with a diffuse MRI pattern when treated upfront with novel agents compared to conventional chemotherapy (47 vs. 24 months; P < 0.001). Diffuse MRI pattern along with ISS-3 and high risk cytogenetics could identify a very high risk group of patients with extremely poor median survival (21 months) and an only 35% probability of 3-year OS. Our study shows that symptomatic myeloma patients with a diffuse MRI pattern at diagnosis very often show high risk cytogenetic abnormalities and are benefiting from upfront novel agent-based therapies. Diffuse MRI pattern in combination with high risk cytogenetics and ISS-3 can identify a subset of myeloma patients with very poor prognosis who may need innovative treatment strategies and possibly more aggressive therapies.

Advances in imaging and the management of myeloma bone disease.

Osteolytic disease is a major complication of multiple myeloma that may lead to devastating skeletal-related events (SREs). Conventional radiography remains the gold standard for the evaluation of bone disease in patients with myeloma. However, whole-body magnetic resonance imaging (MRI) is recommended in patients with normal conventional radiography and should be performed as part of staging in all patients with a solitary plasmacytoma of bone. Urgent MRI is also the diagnostic procedure of choice to assess suspected cord compression, whereas computed tomography can guide tissue biopsy. Positron emission tomography with computed tomography can provide complementary information to MRI, but its use in multiple myeloma must be better defined by further studies. The incorporation of abnormal MRI findings into the definition of symptomatic myeloma also needs to be clarified. Bisphosphonates remain the cornerstone for the management of myeloma bone disease. Intravenous pamidronate and zoledronic acid are equally effective in reducing SREs, whereas zoledronic acid seems to offer survival benefits in symptomatic patients. Caution is needed to avoid adverse events, such as renal impairment and osteonecrosis of the jaw. Novel antiresorptive agents, such as denosumab, have given encouraging results, but further studies are needed before their approval for managing myeloma bone disease. Combination approaches with novel antimyeloma agents, such as bortezomib (which has anabolic effects on bone) with bisphosphonates or with drugs that enhance osteoblast function, such as antidickkopf-1 agents, antisclerostin drugs, or sotatercept, may favorably alter our way of managing myeloma bone disease in the near future.

Degenerative endplate changes of the lumbosacral spine: dynamic contrast-enhanced MRI profiles related to age, sex, and spinal level.

PURPOSE: To investigate differences in perfusion profiles between degenerative endplate marrow changes and normal vertebral marrow in relation to spinal level, age, and sex with dynamic contrast-enhanced magnetic resonance imaging (DCE MRI). MATERIALS AND METHODS: Ninety-two consecutive patients referred for evaluation of low back pain or sciatica, without history of malignant or chronic disease, underwent conventional and DCE MRI of the lumbosacral spine. Fifty-two of them demonstrated degenerative endplate marrow changes. Regions of interest were placed on sites of normal marrow (group A) and degenerative changes (group B) on subtracted images. Fitted time-intensity curves (fTICs) were generated and evaluated for curve pattern. Both groups were stratified into upper (L1-L2) and lower (L3-I1) levels, males and females younger or older than 50 years. Perfusion parameters were calculated and statistically compared for both groups and subgroups. Receiver operator curve (ROC) analysis was also performed. RESULTS: Two fTIC patterns were identified. Perfusion parameters of degenerative changes and normal marrow differed significantly, even when groups were stratified for spinal level, age, and sex (P < 0.05). A time to peak value >108 seconds was characteristic for degenerative changes with sensitivity 69.5% and specificity 84.6%. CONCLUSION: DCE MRI profiles of degenerative endplate marrow changes of the lumbosacral spine differ significantly from normal marrow regardless of spinal level, age, or sex.