Quantitative ultrasound of the calcaneus (QUS): A valuable tool in the identification of patients with non-metastatic prostate cancer requiring screening for osteoporosis.

Non-metastatic prostate cancer (PCa) patients are at increased risk for osteoporosis and fractures mainly due to androgen deprivation therapy (ADT)-associated hypogonadism, but this remains largely underdiagnosed and untreated. In this study, we examine the value of pre-screening calcaneal QUS in identifying patients who should be referred for screening for osteoporosis using dual-energy X-Ray absorptiometry (DXA). In a single-center retrospective cross-sectional cohort study, we analysed data on DXA and calcaneal QUS measurements systematically collected between 2011 and 2013 in all non-metastatic PCa patients attending our Uro-Oncological Clinic at the Leiden University Medical Center. Receiver operating characteristic curves were used to assess the positive (PPV) and negative (NPV) predictive values of QUS T-scores of 0, -1.0, and - 1.8 in identifying DXA-diagnosed osteoporosis (T-scores ≤ - 2.5 and ≤ -2) at lumbar spine and/or femoral neck. Complete sets of data were available in 256 patients, median age 70.9 (53.6-89.5) years; 93.0 % had received local treatment, 84.4 % with additional ADT. Prevalence of osteoporosis and osteopenia was respectively 10.5 % and 53 %. Mean QUS T-score was -0.54 ± 1.58. Whereas PPV at any QUS T-score was <25 %, precluding the use of QUS as surrogate for DXA in screening for osteoporosis, QUS T-scores of -1.0 to 0.0 had a NPV of ≥94.5 % for DXA T-scores ≤ 2.5 and ≤ -2 at any site, confidently identifying patients least likely to have osteoporosis, thereby significantly reducing the number of patients requiring DXA screening for diagnosing osteoporosis by up to two-third. Osteoporosis screening is a significant unmet need in non-metastatic prostate cancer patients treated with ADT, and QUS may represent a valuable alternative pre-screening strategy to overcome logistics, time demands, and economic barriers encountered with current strategies for osteoporosis screening in these patients. Summary: Osteoporosis and associated increased fracture risk are common in non-metastatic prostate carcinoma, mainly due to androgen deprivation therapy, but these often remain underdiagnosed and untreated. We demonstrate that QUS is a safe, less costly pre-screen tool that reduces by up to two-third the number of patients requiring referral for DXA for osteoporosis screening.

Administration of an adeno-associated viral vector expressing interferon-ß in patients with inflammatory hand arthritis, results of a phase I/II study.

OBJECTIVE: Inflammatory hand arthritis (IHA) results in impaired function. Local gene therapy with ART-I02, a recombinant adeno-associated virus (AAV) serotype 5 vector expressing interferon (IFN)-ß, under the transcriptional control of nuclear factor κ-B responsive promoter, was preclinically shown to have favorable effects. This study aimed to investigate the safety and tolerability of local gene therapy with ART-I02 in patients with IHA. METHODS: In this first-in-human, dose-escalating, cohort study, 12 IHA patients were to receive a single intra-articular (IA) injection of ART-I02 ranging 0.3 × 1012-1.2 × 1013 genome copies in an affected hand joint. Adverse events (AEs), routine safety laboratory and the clinical course of disease were periodically evaluated. Baseline- and follow-up contrast enhanced magnetic resonance images (MRIs), shedding of viral vectors in bodily fluids, and AAV5 and IFN-ß immune responses were evaluated. A data review committee provided safety recommendations. RESULTS: Four patients were enrolled. Long-lasting local AEs were observed in 3 patients upon IA injection of ART-I02. The AEs were moderate in severity and could be treated conservative. Given the duration of the AEs and their possible or probable relation to ART-I02, no additional patients were enrolled. No systemic treatment emergent AEs were observed. The MRIs reflected the AEs by (peri)arthritis. No T-cell response against AAV5 or IFN-ß, nor IFN-ß antibodies could be detected. Neutralizing antibody titers against AAV5 raised post-dose. CONCLUSION: Single IA doses of 0.6 × 1012 or 1.2 × 1012 ART-I02 vector genomes were administered without systemic side effects or serious AEs. However, local tolerability was insufficient for continuation. TRIAL REGISTRATION: NCT02727764.

Challenges and opportunities of pharmacological interventions for osteoarthritis: A review of current clinical trials and developments.

Objective: Osteoarthritis (OA) is the most common cause of disability in older adults, and leads to a huge unmet medical need, as no registered disease modifying OA drugs (DMOADs), but only symptomatic treatments, are available. New targets and compounds for these targets, are currently under investigation. The objective of this paper is to provide an overview of compounds under investigation for OA in phase II and III. Design: We performed a review of OA trials for pharmacological interventions registered on the National Library of Medicine ClinicalTrials.gov website with a completion date in 2017 or later. Results: The database search yielded 255 results, of which 184 studies were included in this review. These were structured in compounds targeting pain, immunomodulators, stem cell therapy, platelet rich plasma and DMOADs with cartilage and/or bone resorption modifying properties. Conclusions: The results provide an overview of the fields in development and may include future treatment options for OA, by which a registered DMOADs may become more than a utopic vista. Further knowledge on pathophysiology and new approaches of value-based drug development could be an opportunity for the optimization of drug development in OA.