Prednisone compared to methysprednisolone in the polymyalgia rheumatica treatment

Glucocorticoids (GLs) are the sole therapeutic approach in polymyalgia rheumatica (PMR). An undefined proportion of patients respond only to very high doses of GLs and some seem to respond better to methylprednisolone (MPONE) than to prednisone (PN) or vice versa. Fifty-two PMR patients were randomized (ratio 1/1) to a fixed daily dose of PN (25 mg) or MPONE (20 mg), and the dose was tapered with a fixed scheme at the time of symptomatic relief. The clinical and biochemical assessments were obtained at fixed time points: 2 weeks, and 3, 6, 12 months. A clinical and biochemical remission of PMR was observed in 100 % of the patients on MPONE and in 89 % of the patients on PN. The mean time to achieve full remission after the first dose was significantly (p < 0.05) longer for PN (20.3 days) than for MPONE (15.2 days). This difference was mainly driven by 3 patients in whom the remission was achieved after 26-49 days. The mean levels of serum ACTH and cortisol were very similar in both treatment groups as the slope of their correlations for equivalent steroid doses. PN and MPONE have a similar therapeutic effect on suppression of the HPA axis in PMR patients. The results of this preliminary study suggest that a delayed response to PN may occur. Further studies are warranted in order to verify whether this might be related to variations in 11\u3b2-hydroxysteroid dehydrogenase activity

Bisphosphonates vs infliximab in ankylosing spondylitis treatment.

Objective. The objective of this study was to evaluate if the anti-inflammatory properties of bisphosphonates and their effect on bone turnover could be useful in the treatment of AS.Methods. Sixty patients were consecutively assigned in a 1:1 ratio in a 6-month open-label, single-centre study on active AS to receive monthly i.v. neridronate (100 mg) or standard infliximab (5 mg/kg) therapy.Results. A significant reduction in the mean BASDAI was observed over 6 months of either neridronate (-1.72) or infliximab (-1.62) administration. The BASFI decreased significantly at 3 and 6 months in the neridronate arm, while in the infliximab group a significant reduction at 3 months but not 6 months was observed. The 10-cm visual analogue scale for axial pain decreased significantly and comparably at 3 and 6 months in both groups. No significant differences between treatment arms for all these changes were observed at both 3 months and the final assessment. The BASMI was not significantly modified in the neridronate or infliximab group. No significant variations of BMD were observed in the infliximab group, while in patients treated with neridronate a significant increase was observed at the lumbar spine.Conclusion. High i.v. doses of the amino-bisphosphonate neridronate are as effective as infliximab therapy in reducing disease activity in AS patients, with additional benefits on BMD changes. Further studies to confirm these results over a longer time frame are warranted together with the possibility to explore the long-term efficacy of a combination of lower anti-TNF doses with bisphosphonates

Acute Phase Response After Zoledronic Acid is Associated with Long-Term Effects on White Blood Cells.

We have recently reported a long-lasting decrease in circulating \u3b3\u3b4 T cells in osteoporotic patients on oral amino-bisphosphonates (N-BPs). Here we verify whether these changes are associated with the occurrence of acute phase response (APR) to intravenous (IV) zoledronic acid (ZOL) or changes of other circulating white blood cells (WBC). WBC count was obtained before and 1 year after a single IV administration of 5 mg ZOL in 36 osteoporotic patients (mean age 72 \ub1 9, range 45-86 years) without other relevant diseases; 12 of 36 patients developed the classical APR. After 1 year in the patients who experienced an APR, but not in the others, a significant decrease not only of \u3b3\u3b4 T cells (-30 %), but also of total lymphocytes (-11 %) and eosinophils (-27 %), was observed. The mechanism leading to the observed decrease of circulating lymphocytes and eosinophils remains unclear, but our observation opens a new frontier for the understanding of the immunoeffects of N-BPs

Bone mineral density and bone turnover in premenopausal women with rheumatoid arthritis

Evaluation of bone mineral density and bone turnover in premenopausal women with rheumatoid arthriti

Distinct effect of zoledronate and clodronate on circulating levels of DKK1 and sclerostin in women with postmenopausal osteoporosis.

The coupling of bone formation to bone resorption during treatment of postmenopausal osteoporosis with antiresorbers might be related to changes in Wnt/b-catenin signaling. We compared the effects of two bisphosphonate treatments on two Wnt-inhibitors Sclerostin (SOST) and Dickkopf-related protein 1 (DKK1). The study population included 74 women with postmenopausal osteoporosis participating simultaneously in two multicenter, placebo controlled trials. The patients were randomized to: intramuscular clodronate 100mg/week (CLO) (N=36), and yearly intravenous therapy with 5mg zoledronate (ZOL) (N=18) and placebo (N=20). Bone turnover markers (intact N-propeptide of type I collagen [P1NP], C-terminal telopeptide of type I collagen [CTX]) remained unchanged in the placebo group while they significantly decreased during treatment with the two bisphosphonates, versus both placebo and baseline. In CLO treated patients serum DKK1 remained stable over the entire period of observation while serum SOST levels increased significantly after 12months of treatment both versus placebo group (p<0,005), baseline (p<0,001) and ZOL treated group. In the ZOL group, DKK1 levels increased significantly within one month and for the following 6months and it fell back to baseline values at 12months. The second ZOL infusion was again associated with an increase in DKK1 a month later, although to a lesser extent. In conclusion, in this study we have found that the treatment of postmenopausal osteoporosis with intermittent yearly ZOL is associated with transient and declining increases in DKK1 while continuous treatment with CLO, results in a late increase in serum SOST. These preliminary results and further ad hoc studies might contribute to shed light on our understanding of the bone coupling effects taking place during treatment of osteoporosis with different anti-resorbers or with different treatment regimens

New Mediterranean Biodiversity Records (November 2018)

In the present article, new records are given for 18 species (6 native, 9 alien and 3 cryptogenic), belonging to 5 Phyla (i.e. Chlorophyta, Cnidaria, Annelida, Mollusca and Chordata), from 8 Mediterranean countries: Spain: A large population of Polycerella emertoni reported from the Ebro Delta, the presence of Spinimuricea klavereni is confirmed for the first time in the Catalan coast; Italy: the new record of Cryptonome turcica extends its distribution to the western Mediterranean Sea, the findings of Mawia benovici constitute the southernmost record of this species in the Adriatic Sea; Slovenia: second record of the alien seaslug Cuthona perca in the Mediterranean Sea; Montenegro: Styela plicata communities were recorded in Boka Kotorska Bay; Albania: the native great torpedo ray Tetronarce nobiliana recorded for the first time in Albanian waters; Greece: first record of Lagocephalus sceleratus in the Greek side of the Adriatic, the records of Cassiopea andromeda and Pterois miles are first records of these species from the Ionian Sea, the colonial ascidians Aplidium coeruleum and Didemnum protectum are recorded for the first time in the Eastern Mediterranean, an extremely abundant population of Melibe viridis is found in Messolonghi lagoon, the record of Synchiropus sechellensis is the range expansion of this species in Greek Seas, Acetabularia caliculus is recorded for the first time from Greece; Cyprus: first records of Callionymus filamentosus and Haminoea cyanomarginata from the island; Turkey: the presence of Berthellina citrina in the Mediterranean is confirmed. © 2018 Mediterranean Marine Science

Sclerostin and DKK1 in Primary Hyperparathyroidism

Bone formation is influenced by the Wnt pathway through effects on osteoblast functionality, and these actions are opposed by two antagonists: sclerostin and Dickkopf-1 (DKK1). Decreased levels of serum sclerostin were found after treatment with the PTH analogue teriparatide and in patients with primary hyperparathyroidism (PHPT), while treatment with teriparatide of postmenopausal osteoporosis is associated with increases in serum DKK1. We studied mineral metabolism and Wnt pathway in 21 postmenopausal women affected by PHPT and in 42 age-matched healthy women. Mean serum calcium and PTH were significantly higher and serum phosphates significantly lower in the PHPT group compared with the control group. Serum 25-OH-vitamin D (25OHD) was lower in PHPT patients and 1,25 dihydroxy-vitamin D [1,25(OH)2D] was significantly higher. Patients with PHPT had significantly higher levels of bone alkaline phosphatase (BAP) and of serum C-terminal telopeptides of type I collagene (sCTX). Serum sclerostin in PHPT was significantly lower (-26 %) and serum DKK1 significantly higher (+57 %) than in healthy control subjects. Serum PTH was positively correlated with 1,25OH2D (p < 0.001), BAP (p = 0.036), sCTX (p = 0.003), and DKK1 (p = 0.007) and negatively with 25OHD (p = 0.002) and sclerostin (p = 0.02). In PHPT patients, serum sclerostin was negatively correlated with BAP (p = 0.038) and sCTX (p = 0.07). Patients with PHPT have significantly lower sclerostin and higher DKK1 levels compared with healthy postmenopausal control subjects. Further studies are warranted in order to verify whether the balance between these two opposite effects on Wnt function might help explain the variable bone involvement among patients with PHPT