Treatment of bone marrow edema syndrome with intravenous ibandronate.

BACKGROUND: In this pilot study, we investigated the therapeutic efficacy of intravenous Ibandronate compared to pain medication on the outcome of bone marrow edemas (BME) of the knee and talus. PATIENTS AND METHODS: Fifteen patients with a painful BME of the knee and 15 patients with a BME of the ankle, confirmed on MRI, were enrolled and treated with three ambulatory infusions of each 6 mg Ibandronate (group 1). A control group (group 2) of 10 patients with a BME of the knee and 10 patients with a BME of the talus was treated with pain medication and partial weight bearing. Patients were evaluated clinically at baseline and at 1, 3, 6 and 12 months after therapy start with a visual analog pain-scale (VAS) and specific joint scores (Larson knee- and Mazur ankle-score). BMEs were assessed with MRI at baseline and after 6 months in both groups. RESULTS: In the knee group, the mean VAS pain score decreased from 8.5 at baseline to 1.2 at 12 months (p < 0.0001) in patients treated with Ibandronate and, respectively, from 8.1 to 4.0 in the control group (p < 0.001). In the ankle group, the mean VAS pain score decreased from 8.2 at baseline to 0.9 at 12 months (p < 0.0001) in patients treated with Ibandronate and, respectively, from 7.9 to 3.9 in the control group (p < 0.001). The mean Mazur ankle score increased from 51 to 91 points (p < 0.001) in group 1, and from 52 to 72 points in group 2 (p < 0.01). The mean Larson knee score increased from 54 to 89 points (p < 0.001) at 12 months in group 1, and from 51 to 70 points in group 2 (p < 0.01). For both joints, we observed a significant clinical improvement in the Ibandronate treatment group and in the control group, but functional results were significantly more improved in the Ibandronate treatment group. Only the Ibandronate treatment group showed a significant BME regression at the 6 months MRI follow-up. CONCLUSIONS: Intravenous Ibandronate therapy showed significantly better clinical results and BME regression rates on MR-imaging compared to analgesic medication in combination with partial weight bearing in the treatment of BME of the knee and talus and shortens the natural course of the disease.

Diffusion-weighted imaging for non-invasive and quantitative monitoring of bone marrow infiltration in patients with monoclonal plasma cell disease: a comparative study with histology.

Bone marrow plasma cell infiltration is a crucial parameter of disease activity in monoclonal plasma cell disorders. Until now, the only way to quantify such infiltration was bone marrow biopsy or aspiration. Diffusion-weighted imaging (DWI) is a magnetic resonance imaging-technique that may mirror tissue cellularity by measuring random movements of water molecules. To investigate if DWI is capable of assessing bone marrow cellularity in monoclonal plasma cell disease, we investigated 56 patients with multiple myeloma or monoclonal gammopathy of undetermined significance, and 30 healthy controls using DWI of the pelvis and/or the lumbar spine. In 25 of 30 patients who underwent biopsy, bone marrow trephine and DWI could be compared. Of the patients with symptomatic disease 15 could be evaluated after systemic treatment. There was a positive correlation between the DWI-parameter apparent diffusion coefficient (ADC) and bone marrow cellularity as well as micro-vessel density (P<0·001 respectively). ADC was significantly different between patients and controls (P<0·01) and before and after systemic therapy (P<0·001). In conclusion, DWI enabled bone marrow infiltration to be monitored in a non-invasive, quantitative way, suggesting that after further investigations on larger patient groups this might become an useful tool in the clinical work-up to assess tumour burden.

Whole-body MRI versus whole-body MDCT for staging of multiple myeloma.

OBJECTIVE: The purpose of our study was to compare the detection rate of bone manifestations of multiple myeloma in whole-body MRI compared with MDCT and to assess accuracy in staging. SUBJECTS AND METHODS: Forty-one patients with histologically confirmed myeloma were prospectively examined with a whole-body MDCT protocol and whole-body MRI on a 1.5-T system. The MRI protocol consisted of T1-weighted spin-echo and STIR sequences. For data analysis, the entire skeleton was divided into 61 regions per patient. Image evaluation was performed in a consensus reading by two radiologists blinded to the patients' history, with separate evaluation of each technique. The patients were staged by MRI and MDCT data separately according to the Durie and Salmon PLUS staging system. RESULTS: On MRI, 15 patients showed no involvement. In 26 patients, 975 regions were affected: 21 patients were stage I, two were stage II, and 18 were stage III. On MDCT, 19 patients showed no involvement. In 22 patients, 462 regions were affected. For the detection rate, MRI was statistically superior to MDCT (p < 0.001, Wilcoxon's signed rank test). According to MDCT, 25 patients were stage I, seven were stage II, and nine were stage III. In 21 patients with involvement detected on both methods, MRI showed more extensive disease than MDCT. Eleven patients were understaged with MDCT compared with MRI, which was statistically significant (p < 0.001, chi-square test). CONCLUSION: Whole-body MDCT leads to a significantly lower detection rate and staging in patients with multiple myeloma.

Dynamic contrast-enhanced MRI for assessing the disease activity of multiple myeloma: a comparative study with histology and clinical markers.

PURPOSE: To examine whether parameters of dynamic, contrast-enhanced MRI (DCE MRI) reflect the degree of infiltration and vessel density in corresponding bone marrow biopsy specimens. MATERIALS AND METHODS: The pelvis of 24 patients with multiple myeloma (MM) was examined using contrast-enhanced DCE MRI. Biopsy was obtained from the spina iliaca posterior superior. Using a two-compartment model (assuming one intravascular and one interstitial compartment), the parameters amplitude (A, the maximum, relative signal increase over baseline) and the exchange rate constant (k(ep), describing the redistribution of contrast agent from the interstitial into the intravascular compartment) in the biopsied region were calculated and compared with the histological and clinical data. RESULTS: DCE MRI parameters were significantly higher in lesions with marked infiltration than with mild or no infiltration (P < 0.05). The amplitude normalized to that in the iliac artery (A(n)), but not k(ep), was higher in lesions with high vessel-density at histology (P = 0.01). Higher k(ep) levels were found in presence of increased serum immunoglobulins. CONCLUSION: Increased contrast uptake in the bone marrow of MM patients indicates at least moderate tumor involvement. Furthermore, the contrast enhancement correlates with vessel-density and serum markers of disease activity.

Neovascularization of bone marrow in patients with diffuse multiple myeloma: a correlative study of magnetic resonance imaging and histopathologic findings.

BACKGROUND: The goal of the current study was to assess the correlation between bone marrow histology and contrast enhancement in infiltrative diffuse myeloma. METHODS: Forty-four patients with homogeneous diffuse infiltration of bone marrow by multiple myeloma were examined using magnetic resonance imaging of the spine. The sequence protocol included T1-weighted spin-echo (pre- and post-gadolinium dimeglumine administration) and short-inversion time inversion recovery sequences. The percent increase in signal after intravenous gadolinium administration was calculated in bone marrow from patients with myeloma and from a control group of 86 patients who did not have bone marrow disease. Grade of infiltration with plasma cells, fat cell content, and hematopoietic marrow content were evaluated via histologic assessment of bone marrow, and microvessel density was evaluated via anti-CD34-positive immunostaining. RESULTS: Increased microvessel density was observed in association with increasing plasma cell content (Kruskall-Wallis test: P < 0.0001). Contrast enhancement increased in a stepwise manner according to grade of microvessel density (Mann-Whitney U test: P < 0.05 and P < 0.001 for increases from low to intermediate and intermediate to high grade) and was significantly higher in patients with myeloma compared with control patients (Mann-Whitney U test: P < 0.001). A significant correlation also was found between histologic extent of tumor infiltration and contrast enhancement (Mann-Whitney U test: P < 0.0001). The mean level of contrast enhancement was 18% in the control group, 26% in patients with low-grade infiltration, 49% in patients with intermediate-grade infiltration, and 90% in patients with high-grade infiltration. In addition, fat cell content was found to be inversely correlated with contrast enhancement (chi-square test: P < 0.01). CONCLUSIONS: As a consequence of increased microvessel density, decreased fat cell content, and increased cellularity, the presence of diffuse bone marrow infiltration in patients with multiple myeloma can be verified using gadolinium-enhanced magnetic resonance imaging.

Performance evaluation of automated assays for beta-CrossLaps, N-MID-Osteocalcin and intact parathyroid hormone (BIOROSE Multicenter Study).

INTRODUCTION: Biochemical markers of bone metabolism have been mainly determined manually until now and the precision and accuracy of these methods have not always been satisfactory. This has been shown in several external quality assessment schemes (EQAS). OBJECTIVE AND STUDY DESIGN: A study named BIOROSE was undertaken to evaluate new automated assays for serum markers of bone metabolism. The main focus was to evaluate the assay performance in a multicenter setting with 20 laboratories participating in Germany. The evaluation consists of a familiarization phase to determine precision and accuracy and an EQAS to evaluate the comparability between laboratories. MATERIALS: The parameters beta-CrossLaps (CTX), N-MID-Osteocalcin (OC) and intact parathyroid hormone (PTH) were measured with reagents including calibrators and control sera obtained from Roche Diagnostics, Mannheim, Germany, with electrochemiluminescence immunoassays (ECLIA) on the automated analyzer Elecsys 2010. RESULTS: We calculated for the control samples, PCB 1-3, the mean and median values from the measured values of all participating laboratories and used these as target values. From these target values, a recovery range for the participating laboratories was calculated for beta-CrossLaps, OC and intact PTH of better than 80-126% for PCB 2 and PCB 3, and for PCB 1 (low concentration range) for beta-CrossLaps 79-129%, OC 90-120% and intact PTH 78-126%. The between-day imprecision was 2.4-7.2% for beta-CrossLaps, 1.1-5.9% for OC and 1.7-5.5% for intact PTH in the elevated range (sample PCB 2). In the EQAS, the inter-laboratory imprecision for beta-CrossLaps in the sample with a value of 0.8 ng/ml (above the upper limit of normal, which is 0.6 ng/ml) was 9.8% on day 1 and 9.7% on day 2. CONCLUSION: The performance evaluation of automated assays for beta-CrossLaps, N-MID-Osteocalcin and intact parathyroid hormone in the BIOROSE multicenter study showed that the participating laboratories had no problems in setting up these methods and they yielded results for precision and accuracy that are superior to results achieved in external quality assessment schemes for manually performed methods. In addition, at the clinically important decision level of the upper limit of the normal range, all three tested analytes gave precise results that improved medical decisions.

Acute osteoporotic and neoplastic vertebral compression fractures: fluid sign at MR imaging.

PURPOSE: To evaluate the occurrence, location, and shape of the fluid sign in acute osteoporotic and neoplastic vertebral compression fractures at magnetic resonance (MR) imaging. MATERIALS AND METHODS: The study group comprised 87 consecutive patients with acute vertebral compression fractures due to osteoporotic (n = 52) or neoplastic (n = 35) infiltration. The MR imaging protocol included nonenhanced T1-weighted spin-echo and short inversion time inversion-recovery sequences and a 1.5-T system. Readers blinded to the outcome documented the occurrence, shape, and location of the fluid sign with consensus. The fluid sign was correlated with the cause, age, and severity of the fracture. The diagnosis was confirmed with surgery, follow-up MR imaging, clinical follow-up, or unequivocal imaging findings. Wilcoxon and chi(2) tests were used to assess significance. RESULTS: In fractured vertebral bodies, the fluid sign was adjacent to the fractured end plates and exhibited signal intensity isointense to that of cerebrospinal fluid. The fluid sign was linear (n = 16), triangular (n = 5), or focal (n = 2) and was significantly associated with osteoporotic fractures (21 [40%] of 52; P <.001). The fluid sign occurred in two (6%) of 35 neoplastic compression fractures. Histologic examination demonstrated osteonecrosis, edema, and fibrosis at the site of the fluid sign. There was a tendency toward older fractures exhibiting the fluid sign, but this relationship was not significant (P >.05). In osteoporotic fractures, the fluid sign was significantly associated with fracture severity (P <.05). CONCLUSION: The fluid sign is featured in acute vertebral compression fractures that show bone marrow edema. It can be an additional sign of osteoporosis and rarely occurs in metastatic fractures.

Magnetic resonance imaging as a supplement for the clinical staging system of Durie and Salmon?

BACKGROUND: This study evaluated the prognostic value of a three-grade staging system of spinal involvement using magnetic resonance imaging (MRI) in patients with multiple myeloma and determined its usefulness as an independent parameter in the staging system of Durie and Salmon. METHODS: Seventy-seven previously untreated patients with multiple myeloma underwent MRI of the thoracic and lumbar spine with unenhanced T1-weighted spin echo and short-tau inversion time inversion recovery sequences. The patients were evaluated according to their infiltration patterns and the extent of bone marrow involvement was staged using a three-grade scale: Stage I, no focal or diffuse infiltration; Stage II, 1-10 foci or mild diffuse infiltration; Stage III, more than 10 foci or strong diffuse infiltration. RESULTS: The infiltration patterns had no significant effect on survival. Of 77 patients, 25 would have been understaged using the standard staging system of Durie and Salmon without the findings of MRI and 8 patients would have been understaged if the staging was based only on MRI. The combination of the staging system of Durie and Salmon and MRI was highly significant with respect to survival (P < 0.0001, log rank analysis). MRI staging I-III was independent of the staging system of Durie and Salmon (Cox regression model). CONCLUSIONS: A three-grade staging of spinal MRI provides a significant prognostic tool for patients with multiple myeloma. The authors propose including it in the staging system of Durie and Salmon.