Measuring Drug Therapy Effect on Osteoporotic Fracture Risk by Trabecular Bone Lacunarity: The LOTO Study.

An MRI method providing one parameter (TBLß: trabecular-bone-lacunarity-parameter-ß) that is sensitive to trabecular bone architecture (TBA) changes with aging and osteoporosis is under study as a new tool in the early diagnosis of bone fragility fracture. A cross-sectional and prospective observational study (LOTO: Lacunarity Of Trabecular bone in Osteoporosis) on over-50s women, at risk for bone fragility fracture, was designed to validate the method. From the baseline data, we observed that in women with prevalent vertebral fractures (VF+), TBA was differently characterized by TBLß when osteoporosis treatment is considered. Here we verify the potential of TBLß as an index of osteoporosis treatment efficacy. Untreated (N = 156) and treated (N = 123) women were considered to assess differences in TBLß related to osteoporosis treatment. Prevalent VFs were found in 31% of subjects, 63% of which were under osteoporosis medications. The results show that TBLß discriminates between VF+ and VF- patients (p = 0.004). This result is mostly stressed in untreated subjects. Treatment, drug therapy in particular (89% Bisphosphonates), significantly counteracts the difference between VF+ and VF- within and between groups: TBLß values in treated patients are comparable to untreated VF- and statistically higher than untreated VF+ (p = 0.014) ones. These results highlight the potential role of TBLß as an index of treatment efficacy.

Fractal lacunarity of trabecular bone in vertebral MRI to predict osteoporotic fracture risk in over-fifties women. The LOTO study.

BACKGROUND: Osteoporotic fractures are a major cause of morbidity in the elderly. Menopausal women represent the population with the highest risk of early osteoporosis onset, often accompanied by vertebral fractures (VF). Bone mineral density (BMD) is commonly assessed by dual-energy X-ray absorptiometry (DXA) for osteoporosis diagnosis; however, BMD alone does not represent a significant predictor of fracture risk. Bone microarchitecture, instead, arises as a determinant of bone fragility independent of BMD. High-resolution magnetic resonance imaging (MRI) is an effective noninvasive/nonionizing tool for in vivo characterisation of trabecular bone microarchitecture (TBA). We have previously set up an MRI method able to characterise TBA changes in aging and osteoporosis by one parameter, trabecular bone lacunarity parameter ß (TBLß). Fractal lacunarity was used for TBA texture analysis as it describes discontinuity of bone network and size of bone marrow spaces, changes of which increase the risk of bone fracture. This study aims to assess the potential of TBLß method as a tool for osteoporotic fracture risk. METHODS: An observational, cross-sectional, and prospective study on over-50s women at risk for VF was designed. TBLß, our index of osteoporotic fracture risk, is the main outcome measure. It was calculated on lumbar vertebra axial images, acquired by 1.5 T MRI spin-echo technique, from 279 osteopenic/osteoporotic women with/without prior VF. Diagnostic power of TBLß method, by Receiver Operating Characteristics (ROC) curve and other diagnostic accuracy measurements were compared with lumbar spine DXA-BMD. RESULTS: Baseline results show that TBLß is able to discriminate patients with/without prevalent VF (p = 0.003). AUC (area under the curve from ROC) is 0.63 for TBLß, statistically higher (p = 0.012) than BMD one (0.53). Contribution of TBLß to prevalent VF is statistically higher (p < 0.001) than BMD (sensitivity: 66% vs. 52% respectively; OR: 3.20, p < 0.0001 for TBLß vs. 1.31, p = 0.297 for BMD). Preliminary 1-year prospective results suggest that TBA contribution to incident VF is even higher (sensitivity: 73% for TBLß vs. 55% for BMD; RR: 3.00, p = 0.002 for TBLß vs. 1.31, p = 0.380 for BMD). CONCLUSION: Results from this study further highlight the usefulness of TBLß as a biomarker of TBA degeneration and an index of osteoporotic fracture risk.

Isolated limb infusion chemotherapy with or without hemofiltration for recurrent limb melanoma.

AIM: To better define the efficacy and the safety of intra-arterial infusion performed with or without hemofiltration for recurrent limb melanoma. METHODS: Patients with the following characteristics were included in the study: recurrent limb melanoma not indicated for surgical resection, measurable disease in the extremity, > 18 years, performances status (Eastern Cooperative Oncology Group ) was 0-1 and life expectancy of at least 6 mo. Twenty nine consecutive patients were enrolled in the study. Patients underwent fluoroscopic placement of angiographic arterial and venous catheters to infuse the drug in the artery [isolated limb infusion (ILI)], and to stop the out flow (venous). Melphalan was rapidly infused into the isolated limb via the arterial catheter after the inflation of venous balloon catheter. Then the circulation of the limb was completely blocked with a pneumatic cuff at the root of the limb. Haemofiltration (HF) was available only in the main center, and was performed with an extracorporeal perfusion system, in order to reduce high systemic toxic peaks of drug. RESULTS: Thirty seven ILI were done in 29 cases (31 ILI-HF and 6 ILI) between 2001 and 2014 at Ancona and Pesaro Hospitals, Italy. Clinical outcomes were monitored 30 d after treatment. Eleven patients (38%) received infusion of melphalan alone, 7 (24%) melphalan associated to mitomicin C and 7 (24%) melphalan associated to cisplatin, the remaining 4 were treated with cisplatin, melphalan and epirubicin or cisplatin and mitomicin C. The overall response rate was 66%, in particular, 3 patients (10%) were complete responders and 16 (56%) were partial responders; whereas 7 patients (24%) had stable disease, and 3 (10%) showed progressive disease. Limb toxicity was assessed adopting Wieberdink scale, with evidence of 90% of low grade (I and II) toxicity. CONCLUSION: ILI-HF and ILI are effective and safe treatments for recurrent non-resectable limb melanoma. They present evidence of favorable clinical benefit and is effective in delaying progression.