Effects of alendronate and vitamin D in patients with normocalcemic primary hyperparathyroidism.

UNLABELLED: No data on the pharmacological treatment of normocalcemic hyperparathyroidism (NPHPT) are available. We treated 30 NPHPT postmenopausal women with alendronate/cholecalciferol (treated group) or vitamin D alone (control group). Over 1 year, bone mineral density (BMD) increased significantly in treated group, but not in control group. Both treatments did not affect serum or urinary calcium. INTRODUCTION: Normocalcemic primary hyperparathyroidism (NPHPT) is defined by normal serum calcium and consistently elevated PTH levels after ruling out the causes of secondary hyperparathyroidism. It is likely that subjects with NPHPT may develop kidney and bone disease. As no data on the pharmacological treatment of NPHPT are available, we aimed to investigate the effects of alendronate and cholecalciferol on both BMD and bone biochemical markers in postmenopausal women with NPHPT. Safety of vitamin D was evaluated as secondary endpoint. METHODS: The study was a prospective open label randomized trial comparing 15 postmenopausal women with NPHPT (PMW-NPHPT), treated with oral alendronate plus cholecalciferol (treated group) and 15 PMW-NPHPT treated only with cholecalciferol (control group). Blood samples were obtained at baseline and after 3, 6, and 12 months. Bone turnover markers (BTM) were measured at baseline, 3, and 6 months, respectively. BMD was assessed at baseline and after 12 months. RESULTS: After 1 year of treatment, BMD increased significantly at the lumbar, femoral neck, and hip level in the treated group, but not in the control group (p = 0.001). No differences were found between or within groups in serum calcium, PTH, and urinary calcium levels. BTM significantly decreased in the treated group but not in the control group, at 3 and 6 months (p < 0.001), respectively. No cases of hypercalcemia or hypercalciuria were detected during the study. CONCLUSION: The results of this study indicate that alendronate/cholecalciferol increases BMD in postmenopausal women with NPHPT. Alendronate/cholecalciferol or vitamin D alone does not affect serum or urinary calcium.

Nasal lavage CCL24 levels correlate with eosinophils trafficking and symptoms in chronic sino-nasal eosinophilic inflammation.

OBJECTIVES: The aim of our study was to measure CCL24 (eotaxin-2) levels in nasal lavage fluid of patients with different forms of sinonasal chronic eosinophilic inflammation to verify the relationship with nasal hypereosinophilia and symptoms. METHODS: Patients with nasal hypereosinophilia were randomly recruited and grouped in persistent allergic rhinitis, non-allergic rhinitis with eosinophilia syndrome (NARES) and chronic rhinosinusitis with polyps. Non rhinitic volunteers were recruited as controls. CCL24 concentration was measured by `Quantikine Human CCL24 Immunoassay`. Differential cell counts were performed by microscopic cytological examination of nasal tissue scraped by inferior turbinate. RESULTS: CCL24 levels measured in patient groups were significantly higher compared to control group with the highest levels in NARES patients. Eotaxin- 2 levels were significantly correlated to severity of symptoms and to the percentage of eosinophils in nasal tissue. CONCLUSIONS: We revealed high levels of CCL24 in all patient groups showing a significant correlation with the degree of eosinophilia and clinical symptoms. A prolonged accumulation of CCL24 inside the nasal mucosa may sustain the process of unspecific self-perpetuating eosinophil recruitment pathognomonic of these patients.

[Using parathyroid hormone 1-84 in the treatment of osteoporosis: presentation and comments of main clinical trial]. / Terapia dell'osteoporosi con paratormone 1-84: presentazione e commento dei principali trial clinici.

Osteoporosis and associated fractures associated constitute a real and serious socio-medical problem. The purpose of this research is to report the most important clinical studies regarding the effect of parathyroid hormone PTH 1-84 for osteoporosis. TOP study has demonstrated the antifracture effectiveness of PTH 1-84 in patients of primary prevention and particular attention has been paid to show a clear achievement of the primary end-point that consists in a reduction of the vertebral fracturing event. PATH study has evidenced that the administration for one year of alendronate after one year of PTH 1-84 reduced the risk of osteoporotic fractures. The primary endpoint has been the evaluation of the densitometry values in the femoral and lumbar side and the evaluation of markers of bone turnover. In this case it is possible to assume that the above mentioned therapy could offer benefits in the long term.

Osteoporosis: recent physiopatologic acquisitions and new therapeutic perspectives.

The World Health Organization (WHO) declared osteoporosis "social disease". The present revision of the literature will focus on the recent acquisitions in bone pathophysiology and the efforts in the formulation of new molecules able to change successfully the course of the disease. Osteocyte cell is now thought to be the main biomechanical transducer of bones, able to release sclerostin that produces inhibition on osteosynthesis and on the other hand to release substances like nitrid oxide and prostaglandins that provide a stimulus to osteosynthesis through direct or indirect activation of osteoblasts. In this work the authors analyze the most important clinical trials involving the use of new molecules, like denosumab, integrin avb3 inhibitor, cathepsin k inhibitors, able to interfere in the new osteometabolic pathways. Two trials, phase I and II, have been conducted using denosumab. The endpoint of the first phase was the evaluation of the markers of resorption and bone formation, while the second phase II trial focused on the use of this molecule in double-blind matching placebo and open alendronate with the evaluation of bone mass density (BMD) over one year in lumbar area. Another clinical trial in double-blind versus placebo was carried on and published on the use of a competitive integrin avb3 inhibitor in various dosages for the evaluation of bone mass modification in the lumbar and femoral area and of bone markers modification. Many studies focus on the use of cathepsin k inhibitors. Odanacatib has demonstrated to have worked on dose-dependent increase of densitometric value and to have reduced the bone turnover.

Different structural behaviors evidenced in thaumatin-like proteins: a spectroscopic study.

Three proteins belonging to the thaumatin-like proteins family were compared in this study from a structural point of view: zeamatin, a new recently isolated PR-5 from Cassia didymobotrya and the commercial sweet-thaumatin. The former two proteins possess antifungal activities while commercial thaumatin is well known to be a natural sweetener. Intrinsic fluorescence studies have evidenced that the three proteins behave differently in unfolding experiments showing different structural rigidity. All the three proteins are more stable at slight acidic buffers, but sweet-thaumatin has a major tendency to destructurate itself. Similar observations were made from circular dichroism studies where a structural dependence relationship from the pH and the solvent used confirmed a hierarchic scale of stability for the three proteins. These structural differences should be considered to be significant for a functional role.