Analysis of the evolution of cortical and trabecular bone compartments in the proximal femur after spinal cord injury by 3D-DXA.

Marked trabecular and cortical bone loss was observed at the proximal femur short-term after spinal cord injury (SCI). 3D-DXA provided measurement of vBMD evolution at both femoral compartments and cortical thinning, thereby suggesting that this technique could be useful for bone analysis in these patients. INTRODUCTION: SCI is associated with a marked increase in bone loss and risk of osteoporosis development short-term after injury. 3D-DXA is a new imaging analysis technique providing 3D analysis of the cortical and trabecular bone from DXA scans. The aim of this study was to assess the evolution of trabecular macrostructure and cortical bone using 3D-DXA in patients with recent SCI followed over 12 months. METHODS: Sixteen males with recent SCI (< 3 months since injury) and without antiosteoporotic treatment were included. Clinical assessment, bone mineral density (BMD) measurements by DXA, and 3D-DXA evaluation at proximal femur (analyzing the integral, trabecular and cortical volumetric BMD [vBMD] and cortical thickness) were performed at baseline and at 6 and 12 months of follow-up. RESULTS: vBMD significantly decreased at integral, trabecular, and cortical compartments at 6 months (- 8.8, - 11.6, and - 2.4%), with a further decrease at 12 months, resulting in an overall decrease of - 16.6, - 21.9, and - 5.0%, respectively. Cortical thickness also decreased at 6 and 12 months (- 8.0 and - 11.4%), with the maximal decrease being observed during the first 6 months. The mean BMD losses by DXA at femoral neck and total femur were - 17.7 and - 21.1%, at 12 months, respectively. CONCLUSIONS: Marked trabecular and cortical bone loss was observed at the proximal femur short-term after SCI. 3D-DXA measured vBMD evolution at both femoral compartments and cortical thinning, providing better knowledge of their differential contributory role to bone strength and probably of the effect of therapy in these patients.

Effect of recent spinal cord injury on the OPG/RANKL system and its relationship with bone loss and the response to denosumab therapy.

There is marked bone loss after spinal cord injury (SCI); however, its pathogenesis and clinical management remain unclear. The increased circulating levels of receptor activator of nuclear factor kB ligand (RANKL) associated with bone loss shortly after SCI and the prevention of bone loss with denosumab treatment suggest a contributory role of RANKL in SCI-induced osteoporosis. INTRODUCTION: Bone turnover and bone loss are markedly increased shortly after SCI. However, the pathogenesis and clinical management of this process remain unclear, especially the role of the osteoprotegerin (OPG)/RANKL system in this disorder. The aim of this study was to analyze serum levels of OPG and RANKL in bone loss associated with recent SCI and the effect of denosumab treatment on these mediators. METHODS: Twenty-three males with recent complete SCI were prospectively included. Serum OPG and RANKL levels, bone turnover markers (PINP, bone ALP, CTX), and bone mineral density (BMD) were assessed at baseline, at 6 months of follow-up, prior to initiating denosumab, and 6 months after treatment. The results were compared with a healthy control group. RESULTS: At baseline, SCI patients showed higher RANKL levels vs. controls which were correlated with days-since-SCI and total hip BMD loss at 6 months. OPG levels were similar to controls at baseline. After denosumab treatment, OPG showed no changes, whereas RANKL levels became undetectable in 67% of patients. Patients with undetectable RANKL during treatment showed better response in femoral BMD and bone markers vs. patients with detectable RANKL at 6 months of denosumab. Increased parathormone (PTH) levels during treatment were negatively correlated with RANKL changes. CONCLUSIONS: RANKL levels are increased after SCI and related to BMD loss at the proximal femur, becoming undetectable after denosumab treatment. The effect of denosumab on preventing sublesional bone loss, especially in patients with undetectable levels during treatment, suggests a contributory role of RANKL in this process.

Denosumab increases sublesional bone mass in osteoporotic individuals with recent spinal cord injury.

UNLABELLED: Osteoporosis is a frequent complication related to spinal cord injury (SCI), and data on osteoporosis treatment after SCI is scarce. Treatment with denosumab increases lumbar and femoral BMD and decreases bone turnover markers in individuals with recent SCI. This drug may be a promising therapeutic option in SCI-related osteoporosis. INTRODUCTION: Osteoporosis development is a frequent complication related to SCI, especially at the sublesional level. Nevertheless, data on osteoporosis treatment after SCI is scarce, particularly short term after injury, when the highest bone loss is produced. The aim of this study was to analyze the efficacy of denosumab in the treatment of SCI-related osteoporosis. METHODS: Fourteen individuals aged 39 ± 15 years with osteoporosis secondary to recent SCI (mean injury duration 15 ± 4 months) were treated with denosumab for 12 months. Bone turnover markers (BTMs) (PINP, bone ALP, sCTx), 25-hydroxyvitamin D (25OHD) levels and bone mineral density (BMD) at the lumbar spine (LS), total hip (TH), and femoral neck (FN) were assessed at baseline and at 12 months. All participants received calcium and vitamin D supplementation. RESULTS: At 12 months, SCI denosumab-treated participants showed a significant increase in BMD at TH (+2.4 ± 3.6 %, p = 0.042), FN (+3 ± 3.6 %, p = 0.006), and LS (+7.8 ± 3.7 %, p < 0.001) compared to baseline values. Denosumab treatment was associated with significant decreases in BTMs (bone ALP -42 %, p < 0.001; PINP -58 %, p < 0.001, sCTx -57 %, p = 0.002) at 12 months. BMD evolution was not related to BTM changes or 25OHD serum levels. No skeletal fractures or serious adverse events were observed during follow-up. CONCLUSIONS: Treatment with denosumab increases lumbar and femoral BMD and decreases bone turnover markers in individuals with recent SCI. This drug may be a promising therapeutic option in SCI-related osteoporosis.

Magnesium sulphate and (123)I-MIBG in pheochromocytoma: Two useful techniques for a complicated disease.

Pheochromocytoma is a tumour of the chromaffin tissue. It may, through catecholamine release, have deleterious effects on myocardial structure. A 48-year-old woman with a history of hypertension and type II diabetes mellitus (ASA II) was diagnosed of pheochromocytoma-induced myocarditis, which caused severe cardiogenic shock, with an ejection fraction of 20%. Extreme blood pressure swings required aggressive therapy with vasoactive drugs (norepinephrine and dopamine) and an intra-aortic balloon pump, despite which severe haemodynamic instability persisted. Finally, the use of magnesium sulphate allowed for cardiovascular stabilization and weaning off vasoactive drugs prior to surgery. (123)I-metaiodobenzylguanidine scintigraphy helps not only to functionally confirm tumour tissue, but also to assess severity and prognosis of cardiac failure. Prognosis of pheochromocytoma-induced heart failure can be very poor. The use of these two well-known and relatively simple 'tools' for treatment and prognosis is a helpful option to keep in mind.

Risk factors for the development of osteoporosis after spinal cord injury. A 12-month follow-up study.

UNLABELLED: Spinal cord injury (SCI) has been associated with a marked bone loss after injury and a consequent increased risk of osteoporosis. The evaluation of bone mineral density shortly after SCI is a simple and effective method for predicting the development of osteoporosis during the first year after SCI. INTRODUCTION: Spinal cord injury (SCI) has been associated with a marked bone loss after injury and a consequent increased risk of osteoporosis and fractures. The aim of this study was to analyze the factors associated with osteoporosis development short-term after SCI. METHODS: We included patients with complete recent SCI (<6 months) evaluating bone turnover markers (P1NP, bone ALP, and sCTx), 25-OH-vitamin D (25OHD) levels, and lumbar and femoral BMD (Lunar, Prodigy) at baseline, 6 and 12 months after SCI. The risk factors for osteoporosis analyzed included the following: age, gender, BMI, toxic habits, bone turnover markers, 25OHD levels, lumbar and femoral BMD, level, severity and type of SCI, and days-since-injury. Osteoporosis was defined according to WHO criteria. RESULTS: Thirty-five patients aged 35 ± 16 years were included, and 52 % developed osteoporosis during the 12-month follow-up. These latter patients had lower BMD values at femur and lumbar spine and higher bone turnover markers at baseline. On multivariate analysis, the principal factors related to osteoporosis development were as follows: total femur BMD <1 g/cm(2) (RR, 3.61; 95 % CI 1.30-10.06, p = 0.002) and lumbar BMD <1.2 g/cm(2) at baseline (0.97 probability of osteoporosis with both parameters under these values). Increased risk for osteoporosis was also associated with increased baseline values of bone ALP (>14 ng/mL) (RR 2.40; 95 % CI 1.10-5.23, p = 0.041) and P1NP (>140 ng/mL) (RR 3.08; 95 % CI 1.10-8.57, p = 0.017). CONCLUSIONS: The evaluation of BMD at the lumbar spine and femur short-term after SCI is a simple, effective method for predicting the development of osteoporosis during the first year after SCI. Our results also indicate the need to evaluate and treat these patients shortly after injury.

Efficacy of low doses of pamidronate in osteopenic patients administered in the early post-renal transplant.

UNLABELLED: This study evaluates the efficacy of low doses of pamidronate after renal transplantation to prevent bone loss in osteopenic patients. Results show that pamidronate is safe and significantly reduced spinal bone loss when administered immediately after renal transplantation. INTRODUCTION: The purpose of this work is to evaluate the efficacy of two intravenous infusions of pamidronate in the immediate post-transplant period in a renal transplant (RT) population. METHODS: In this 12-month, randomized, double-blind, multicenter trial, 39 kidney recipients with diagnosed osteopenia received two doses of 30 mg of disodium pamidronate (n = 24) or placebo (n = 15), at surgery and 3 months post-RT. All patients received calcium and vitamin D. Bone density of the lumbar spine and total femur was measured by dual-energy X-ray absorptiometry (DXA) and X-rays were performed at RT, 6 and 12 months post-RT. Biochemical and hormonal determinations were performed before and after treatment. RESULTS: Pamidronate significantly reduced spinal bone loss, but no significant benefit was found for the incidence of fractures. Elevated baseline intact parathyroid hormone (iPTH) and bone remodeling markers returned to normal levels 3 months post-RT. However, normal procollagen type I N propeptide (PINP) concentrations were only maintained in the pamidronate group. After RT, a comparable graft function was observed in both groups according to creatinine values, 25-hydroxyvitamin-D (25-OH-D) levels were improved, and serum calcium levels normalized after a transient fall during the first 3 months. CONCLUSION: A low dose of pamidronate prevents bone loss in osteopenic patients when administered immediately after RT.

Monitoring system for isolated limb perfusion based on a portable gamma camera.

BACKGROUND: The treatment of malignant melanoma or sarcomas on a limb using extremity perfusion with tumour necrosis factor (TNF-alpha) and melphalan can result in a high degree of systemic toxicity if there is any leakage from the isolated blood territory of the limb into the systemic vascular territory. Leakage is currently controlled by using radiotracers and heavy external probes in a procedure that requires continuous manual calculations. The aim of this work was to develop a light, easily transportable system to monitor limb perfusion leakage by controlling systemic blood pool radioactivity with a portable gamma camera adapted for intraoperative use as an external probe, and to initiate its application in the treatment of MM patients. METHODS: A special collimator was built for maximal sensitivity. Software for acquisition and data processing in real time was developed. After testing the adequacy of the system, it was used to monitor limb perfusion leakage in 16 patients with malignant melanoma to be treated with perfusion of TNF-alpha and melphalan. RESULTS: The field of view of the detector system was 13.8 cm, which is appropriate for the monitoring, since the area to be controlled was the precordial zone. The sensitivity of the system was 257 cps/MBq. When the percentage of leakage reaches 10% the associated absolute error is +/-1%. After a mean follow-up period of 12 months, no patients have shown any significant or lasting side-effects. Partial or complete remission of lesions was seen in 9 out of 16 patients (56%) after HILP with TNF-alpha and melphalan. CONCLUSION: The detector system together with specially developed software provides a suitable automatic continuous monitoring system of any leakage that may occur during limb perfusion. This technique has been successfully implemented in patients for whom perfusion with TNF-alpha and melphalan has been indicated.

Is there a role for (99m)Tc-anti-CEA monoclonal antibody imaging in the diagnosis of recurrent colorectal carcinoma?

AIM: To evaluate the usefulness of immunoscintigraphy with an anti-CEA monoclonal antibody fragment labelled with (99m)Tc for early detection of colorectal recurrence in patients with rising serum CEA levels. METHODS: Fifty-one consecutive patients (27 women, 24 men) with colorectal cancer (mean age 68.9+/-10.2 years) and rising CEA levels (16.2+/-18.2 ng/ml) were prospectively studied. Two immunoscintigraphy studies were performed in 8 patients (n=59). Immunoscintigraphy was performed after i.v. injection of 925 MBq of anti-CEA monoclonal antibody. Planar images of the thorax, abdomen and pelvis, as well as SPECT of the abdomen and pelvis were obtained at 4 and 24 hours after injection. In all cases an abdominal CT scan was previously performed. Findings were validated by histopathological analysis (28 cases) or by imaging and clinical follow-up of at least 6 months following the immunoscintigraphy (31 cases). RESULTS: Forty-one patients did not show recurrence during follow-up. We found 18 cases with confirmed diagnosis of extrahepatic abdominal or pelvic diseases, 11 cases with liver metastases, 9 in the thorax and 2 in the bone. In patients with pelvic and extrahepatic abdominal disease, immunoscintigraphy was positive in 18 cases (14 true positive, 4 false positive). From the 14 true positive only 7 cases had been detected by CT. Immunoscintigraphy was negative in the remaining 41 cases (37 true negative, 4 false negative). Therefore, the sensitivity and specificity for immunoscintigraphy in extrahepatic abdominal and pelvic disease were 78% and 90%, respectively. CT results showed a lower sensitivity of 61% (p<0.05) and specificity of 83%. Liver metastases were detected by CT in 9 cases, but only 2 of these were identified using immunoscintigraphy. CONCLUSION: Scintigraphy with anti-CEA monoclonal antibody fragment labelled with (99m)Tc is superior to CT for the detection of pelvic and extrahepatic abdominal recurrence of colorectal cancer, while CT is more sensitive in the detection of liver and lung metastases. Immunoscintigraphy has a limited usefulness in the detection of distant metastases, but it may be helpful in the diagnosis of suspected colorectal recurrence in patients with non-conclusive CT findings, when FDG-PET is not available.

Radioimmunoguided surgery of colorectal carcinoma with an 111In-labelled anti-TAG72 monoclonal antibody.

Radioimmunoscintigraphy (RIS) and radioimmunoguided surgery (RIGS) were assessed for their usefulness in patients with colorectal carcinoma. Twenty-nine patients (18 primary tumours, 10 with a suspicion of recurrence and one colonic diverticulitis) were studied. Radioimmunoscintigraphy was performed 48 and 72 h after the injection of an anti-TAG72 monoclonal antibody (CYT-103) labelled with 111In. Radioimmunoguided surgery was performed between 72 and 96 h post-injection. During surgery, a systematic screening was performed with a hand-held gamma detecting probe and a surgical index (tumour-to-normal tissue) was obtained. There were statistically significant differences between counts in normal tissue versus tumour (P < 0.001) and RIGS was considered positive for the detection of tumour if the ratio between the counts in the area suspicious of tumour and the counts in the normal tissue was greater than 1.5. The overall sensitivity for RIS and RIGS was 71.4% (55.6% in primary tumours and 100% in recurrences) and 82.1% (83.3% in primary tumours and 80% in recurrences), respectively. Radioimmunoguided surgery changed the surgical procedure in two cases with small tumour deposits. Occult regional lymph node involvement in primary tumours was not found; therefore, RIGS, as a complementary technique to RIS, is particularly useful in recurrences and can help the surgeon in the resection of small tumour deposits which are difficult to localize.

Radioimmunoscintigraphy of colorectal carcinoma with a 111In-labelled anti-TAG-72 monoclonal antibody.

Radioimmunoscintigraphy (RIS) of colorectal carcinoma with a 111In-labelled anti-TAG-72 monoclonal antibody (CYT-103) has been performed in 24 patients with five primary lesions and 10 suspicious of recurrence (in one of these patients two RIS were made). Histopathological confirmation of the disease and surgical liver examination were carried out in all primary tumours and in 12 possible recurrences. In the remaining eight patients a final diagnosis was established according to the clinical course and other diagnostic procedures. Planar and tomographic scans were obtained at 48 and 72 h postinjection in all patients. All primary tumours were detected by RIS. In the group with recurrences confirmed pathologically the results were nine true positive, two true negative and one false positive in a patient affected only with liver disease. The nine true positive studies corresponded to four positive by computed tomography (CT), four negative by CT and one nonconclusive by CT. Surgical liver examination results were 15 true negative and two false negative. No correlation was found between serum levels of carcinoembryonic antigen or TAG-72 and the detection of the lesions. In 10 patients human anti-mouse antibody (HAMA) levels were studied. In conclusion, RIS with an anti-TAG-72 monoclonal antibody is a useful technique for the study and localization of colorectal tumours, mainly in cases of recurrence, being also indicated in patients with normal TAG-72 serum levels.

Radioimmunoscintigraphy of colorectal carcinoma with a 99Tcm-labelled anti-CEA monoclonal antibody (BW 431/26).

Radioimmunoscintigraphy (RIS) with BW 431/26 monoclonal antibody (MoAb) labelled with 99Tcm (962 MBq) has been performed in 64 patients with colorectal carcinoma, one of them with two independent tumours. The group consisted of 46 primary lesions, 15 pelvic recurrences and four suspected recurrences which were shown to be liver metastases. Imaging of liver was obtained in all patients, but surgical liver examination was performed in only 56 of them. Planar scans were obtained at 4 and 24 h postinjection. Tomographic images were also performed in five patients. The final diagnosis was confirmed in all patients by their clinical course and by findings at surgery and pathology. A comparative study between the RIS results and the final diagnosis gave a global sensitivity in primary tumours and pelvic recurrences of 59.7% with an accuracy of 59.0%. When rectal tumours were excluded, the results were 81.1 and 84.9%, respectively. In liver metastases the sensitivity was 50%, with an accuracy of 85.7% and a specificity of 100%. No correlation has been found between CEA serum levels and lesion detection. In conclusion, RIS is a useful technique for the study and localization of colorectal tumours, being also indicated in patients with normal carcinoembryonic antigen (CEA) serum levels and clinical suspicion of illness.

99Tcm-HMPAO leucocyte scintigraphy in the diagnosis of bone infection.

The utility of 99Tcm-HMPAO leucocytes has been studied in combination with 99Tcm-MDP bone scanning in the diagnosis of bone infection in a series of 50 patients with a clinical suspicion of bone infection. Thirty-three patients were referred to our Service from the Department of Orthopaedic Surgery (Group A) and seventeen from the Infectious Disease Unit (Group B). A total of 52 lesion sites were studied. The leucocyte and bone studies were performed within four days. The leucocyte scan was obtained at 30-60 min and 4-6 h after i.v. injection of 370 +/- 74 MBq of 99Tcm-HMPAO leucocytes. After confirming the scintigraphic findings, the results obtained were: Group A, 12 true positive, 21 true negative and 2 false positive; and in Group B, 5 true positive, 9 true negative and 4 false negative. The overall sensitivity was 80.9% with a specificity of 93.7%. Although the high bone marrow activity seen with 99Tcm-HMPAO leucocytes may reduce sensitivity, very good results were obtained in bone infection. The use of 99Tcm means great progress in the radiolabelling of white blood cells in terms of availability and better image quality. The combination of 99Tcm-HMPAO leucocytes and 99Tcm-MDP can be recommended as one of the most suitable methods for use in the diagnosis of bone infection, especially in patients with previous bone disease.

[Immunoscintigraphy with monoclonal antibody Tc99m BW 431/26 in the diagnosis of colorectal carcinoma]. / Inmunogammagrafía con el anticuerpo monoclonal 99mTc BW 431/26 en el diagnóstico del carcinoma colorrectal.

BACKGROUND: The use of monoclonal antibodies against tumoral antigens marked with radioactive isotopes is the basis of immunoscintigraphy. The specificity of the technique is high owing to its intrinsic characteristics. METHODS: 40 patients with colorectal cancer who were awaiting surgery were evaluated by immunoscintigraphy. The group consisted of 34 primary diseases and 7 recurrences. Two days before surgery the specific monoclonal antibody BW 431/26 (Behringwerke, FRG) labeled with 99mTc was injected and scintigraphic images were obtained 4 and 24 hours after its administration. RESULTS: The following results were found after a comparison of the data with those from other diagnostic procedures and surgical findings: in primary disease, sensitivity (S) was 59% and accuracy (A) was 56% (these rates increased to 82% and 75%, respectively, when rectal tumors were excluded). For hepatic metastases, S was 44% and A was 85%. In the recurrence group the results were: 4 true positives, 2 false negatives (in the rectum), and one false positive. CONCLUSIONS: These results confirm the validity of immunoscintigraphy in patients with colorectal carcinoma. This test may supplement the information of other diagnostic tests, particularly when these have more limitations as it is the case for recurrences.