Enhanced Formation of Nanometric Titanium Cones by Incorporation of Titanium, Tungsten and/or Iron in a Helium Ion Beam

Surface patterning of bio-compatible titanium (Ti) shows a growing interest in the medical field. The engineering of material surfaces can achieve bactericidal properties and osteointegration improvements in order to develop medical implants. Spikes-like surface morphologies have already demonstrated the development of promising bactericidal properties. A barely new method to produce nanometric-sized cones on titanium consists of helium (He) ion irradiation using low energies ( 100 eV) and temperatures comprised between 0.25 T/T 0.5 (with T being the melting temperature of the material). Ti, iron (Fe) and/or tungsten (W) were incorporated in a He beam, and their amounts were quantified using X-ray Photoelectron Spectroscopy (XPS). The He ion energy was varied from 70 and 120 eV, the surface temperatures from 571 to 651 K for fluences approximately equal to 1024 m−2. After irradiation, the surface morphology was characterized using Scanning Electron Microscopy (SEM) and Focused Ion Beam (FIB). This study demonstrated the capability for irradiated Ti surfaces to form cones with tunable density, aspect ratio, and heights with the incorporation of Ti, Fe and/or W in a He ion. Additionally, the growth rate of the cones was enhanced by about 30 times in comparison to pure He irradiation as a function of the chosen materials introduced in the He beam

The effects of palovarotene in patients with fibrodysplasia ossificans progressiva : a plain language summary

What is this summary about? This is a plain language summary of an article originally published in the Journal of Bone and Mineral Research. People with fibrodysplasia ossificans progressiva (FOP) become physically disabled over time as new bone forms in places where it is not usually found, such as in muscles and ligaments. Until recently, there were no treatments for FOP that had been proven through clinical trials; however, a drug called palovarotene has been tested in clinical trials and may be effective. Here, we describe the MOVE trial, which investigated how effectively palovarotene works, as well as its safety in treating patients with FOP. What were the results? Results from MOVE suggest that palovarotene may reduce extra bone formation outside the normal skeleton. Patients with FOP who took palovarotene formed less new bone than those who did not take palovarotene. The most common side effects involved the skin, and included dryness and irritation. Some children who were still growing when they took palovarotene had a side effect that resulted in the (normal) growth of their skeleton stopping too soon. What do the results of the trial mean? Palovarotene may be a useful treatment option for FOP. Patients, caregivers, and doctors would need to consider the benefits and risks of treatment with palovarotene, particularly with growing children.This is a plain language summary of an article originally published in the Journal of Bone and Mineral Research: Pignolo, R.J., Hsiao, E.C., Al Mukaddam, M., Baujat, G., Berglund, S.K., Brown, M.A., Cheung, A.M., De Cunto, C., Delai, P., Haga, N., Kannu, P., Keen, R., Le Quan Sang, K.-H., Mancilla, E.E., Marino, R., Strahs, A. and Kaplan, F.S. (2023), Reduction of New Heterotopic Ossification (HO) in the Open-Label, Phase 3 MOVE Trial of Palovarotene for Fibrodysplasia Ossificans Progressiva (FOP). J Bone Miner Res, 38: 381-394. https://doi.org/10.1002/jbmr.4762</p

Reduction of new heterotopic ossification (HO) in the open-label, phase 3 MOVE trial of palovarotene for fibrodysplasia ossificans progressiva (FOP)

Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare, severely disabling genetic disorder of progressive heterotopic ossification (HO). The single-arm, open-label, phase 3 MOVE trial (NCT03312634) assessed efficacy and safety of palovarotene, a selective retinoic acid receptor gamma agonist, in patients with FOP. Findings were compared with FOP natural history study (NHS; NCT02322255) participants untreated beyond standard of care. Patients aged ≥4 years received palovarotene once daily (chronic: 5 mg; flare-up: 20 mg for 4 weeks, then 10 mg for ≥8 weeks; weight-adjusted if skeletally immature). The primary endpoint was annualized change in new HO volume versus NHS participants (by low-dose whole-body computed tomography [WBCT]), analyzed using a Bayesian compound Poisson model (BcPM) with square-root transformation. Twelve-month interim analyses met futility criteria; dosing was paused. An independent Data Monitoring Committee recommended trial continuation. Post hoc 18-month interim analyses utilized BcPM with square-root transformation and HO data collapsed to equalize MOVE and NHS visit schedules, BcPM without transformation, and weighted linear mixed-effects (wLME) models, alongside prespecified analysis. Safety was assessed throughout. Eighteen-month interim analyses included 97 MOVE and 101 NHS individuals with post-baseline WBCT. BcPM analyses without transformation showed 99.4% probability of any reduction in new HO with palovarotene versus NHS participants (with transformation: 65.4%). Mean annualized new HO volume was 60% lower in MOVE versus the NHS. wLME results were similar (54% reduction fitted; nominal p = 0.039). All palovarotene-treated patients reported ≥1 adverse event (AE); 97.0% reported ≥1 retinoid-associated AE; 29.3% reported ≥1 serious AE, including premature physeal closure (PPC)/epiphyseal disorder in 21/57 (36.8%) patients aged &lt;14 years. Post hoc computational analyses using WBCT showed decreased vertebral bone mineral density, content, and strength, and increased vertebral fracture risk in palovarotene-treated patients. Thus, post hoc analyses showed evidence for efficacy of palovarotene in reducing new HO in FOP, but high risk of PPC in skeletally immature patients