Long-Term Efficacy of Intensive Zoledronate Therapy and Predictors of Retreatment in Paget’s Disease of Bone

Despite the current debate on the best therapeutic approach, i.e. symptomatic vs intensive strategy, one zoledronate (Zol) infusion is effective in most patients with Paget’s disease of bone (PDB), whereas few need retreatment, whose predictors are not well established. We aimed to evaluate long-term efficacy of intensive Zol therapy and predictors of retreatment in PDB. Pagetic complications, clinical and biochemical response to Zol together with frequency of retreatment were retrospectively assessed in forty-seven PDB patients (age, mean ± SD: 72.5 ± 8.9 years, M/F: 24/23; symptomatic/asymptomatic: 16/31). Statistical analysis for retreatment prediction were based on Mann–Whitney U test, Pearson’s Χ2 and ROC curve analysis. During seven-year follow-up, all patients achieved pain relief and only one underwent arthroplasty. Bone alkaline phosphatase (BAP) detected three non-responder (6%) and six relapsing (13%) patients needing retreatment. Retreated patients had less old age (66.1 ± 11.2 vs 74.0 ± 7.7 years), higher frequency of polyostotic disease (78% vs 40%) and higher baseline (96.5 ± 24.8 vs 44.9 ± 27.7 mcg/l) and post-Zol nadir BAP levels (24.7 ± 24.1 vs 8.1 ± 4.1 mcg/l) than patients treated once (p < 0.05 for all comparisons). In multivariate analysis both serum baseline and post-Zol nadir BAP significantly predicted retreatment (OR 1.09, 95%CI 1.01–1.17 and 1.29, 1.03–1.62, respectively), with ROC curve analysis showing the greatest accuracies for threshold values of 75.6 and 9.9 mcg/l (sensitivity 88 and 90%, specificity 94 and 86%, AUC 0.92 and 0.93, respectively). Our data in mostly asymptomatic, metabolically active PDB patients treated with intensive Zol therapy show a negligible incidence of pagetic complications and long-term optimal disease control, with BAP being the best predictor of retreatment

Late metamorphic veins with dominant PS-15 polygonal serpentine in the Monte Avic ultramafite

The ultramafic body of Monte Avic (Aosta Valley, Western Alps, Italy) consists of antigorite serpentinite and Ti-clinohumite metadunite. They host late metamorphic veins, up to a couple of centimeters thick, compact, and homogeneous, with a “porcelain” appearance. Vein colors range from yellowish to light greenish, light yellowish fading to white, or rare orange. The veins consist of 15-sector PS-15 polygonal serpentine, with chemical composition Mg2.85 Fe0.08 Si2.05 O7.05 [OH]3.95. Recognition of this unusual phase is supported by diagnostic satellite reflections in the X-ray powder diffraction pattern (e.g., at dobs of 2.502, 2.336, 2.151, and 1.966 Å) TEM images (showing 15-sector polygonal fibers, mostly 200 nm in diameter and a few µm in length, forming a randomly oriented felt) and a µ-Raman wavenumber, matching previous data. This different evidence affords the successful distinction of PS-15 and PS-30, alternatively using TEM images, X-ray powder diffraction, or the low- and high-wavenumber µ-Raman spectra. At Monte Avic, the vein emplacement was accompanied by significant fluid pressure, as suggested by deformation and dismembering of the host rock, with PS-15 grown within isotropic stress microenvironments characterized by fluid-filled voids. Random growth of the mass-fiber polygonal serpentine was favored by low-strain conditions. PS-15 veins formed at the end of the long polyphase Alpine orogenic evolution, with hydrous fluids possibly deriving from serpentinite dehydration in the depth.</p